Obesity-induced insulin resistance is the hallmark of metabolic syndrome,and chronic,low-grade tissue inflammation links obesity to insulin resistance through the activation of tissue-infiltrating immune cells.Current...Obesity-induced insulin resistance is the hallmark of metabolic syndrome,and chronic,low-grade tissue inflammation links obesity to insulin resistance through the activation of tissue-infiltrating immune cells.Current therapeutic approaches lack efficacy and immunomodulatory capacity.Thus,a new therapeutic approach is needed to prevent chronic inflammation and alleviate insulin resistance.Here,we synthesized a tetrahedral framework nucleic acid(tFNA)nanoparticle that carried resveratrol(RSV)to inhibit tissue inflammation and improve insulin sensitivity in obese mice.The prepared nanoparticles,namely tFNAs-RSV,possessed the characteristics of simple synthesis,stable properties,good water solubility,and superior biocompatibility.The tFNA-based delivery ameliorated the lability of RSV and enhanced its therapeutic efficacy.In high-fat diet(HFD)-fed mice,the administration of tFNAs-RSV ameliorated insulin resistance by alleviating inflammation status.tFNAs-RSV could reverse M1 phenotype macrophages in tissues to M2 phenotype macrophages.As for adaptive immunity,the prepared nanoparticles could repress the activation of Th1 and Th17 and promote Th2 and Treg,leading to the alleviation of insulin resistance.Furthermore,this study is the first to demonstrate that tFNAs,a nucleic acid material,possess immunomodulatory capacity.Collectively,our findings demonstrate that tFNAs-RSV alleviate insulin resistance and ameliorate inflammation in HFD mice,suggesting that nucleic acid materials or nucleic acid-based delivery systems may be a potential agent for the treatment of insulin resistance and obesity-related metabolic diseases.展开更多
Because of complexity and non-predictability of the tunnel surrounding rock, the problem with the determination of the physical and mechanical parameters of the surrounding rock has become a main obstacle to theoretic...Because of complexity and non-predictability of the tunnel surrounding rock, the problem with the determination of the physical and mechanical parameters of the surrounding rock has become a main obstacle to theoretical research and numerical analysis in tunnel engineering. During design, it is a frequent practice, therefore, to give recommended values by analog based on experience. It is a key point in current research to make use of the displacement back analytic method to comparatively accurately determine the parameters of the surrounding rock whereas artificial intelligence possesses an exceptionally strong capability of identifying, expressing and coping with such complex non-linear relationships. The parameters can be verified by searching the optimal network structure, using back analysis on measured data to search optimal parameters and performing direct computation of the obtained results. In the current paper, the direct analysis is performed with the biological emulation system and the software of Fast Lagrangian Analysis of Continua (FLAC3D. The high non-linearity, network reasoning and coupling ability of the neural network are employed. The output vector required of the training of the neural network is obtained with the numerical analysis software. And the overall space search is conducted by employing the Adaptive Immunity Algorithm. As a result, we are able to avoid the shortcoming that multiple parameters and optimized parameters are easy to fall into a local extremum. At the same time, the computing speed and efficiency are increased as well. Further, in the paper satisfactory conclusions are arrived at through the intelligent direct-back analysis on the monitored and measured data at the Erdaoya tunneling project. The results show that the physical and mechanical parameters obtained by the intelligent direct-back analysis proposed in the current paper have effectively improved the recommended values in the original prospecting data. This is of practical significance to the appraisal of stability and informationization design of the surrounding rock.展开更多
The present study investigated the effect of treatment with methanolic extracts of Yin- and Yang-Chinese tonifying herbs on concanavalin A (Con A)/lipopolysaccharide (LPS)-stimulated splenocyte proliferation (adaptive...The present study investigated the effect of treatment with methanolic extracts of Yin- and Yang-Chinese tonifying herbs on concanavalin A (Con A)/lipopolysaccharide (LPS)-stimulated splenocyte proliferation (adaptive immunity) and natural killer (NK) cell activity (innate immunity) in an ex vivo mouse model. The results indicated that while treatment with most Yin herbal extracts potentiated the Con A/LPS-stimulated splenocyte proliferation, only Yang (but not Yin) herbal extracts stimulated NK cell activity. The differential effects of Yin- and Yang-Chinese tonifying herbs on innate and adaptive immunity are consistent with the Chinese medicine theory which depicts the Yin and Yang functional components of Zheng Qi (vital energy), with the Yang component being responsible for the first line of defense against invading microorganisms (i.e., innate immunity) and the Yin oner serving as a follow-up defensive response (adaptive immunity).展开更多
Schisandrae Fructus, containing schisandrin B (Sch B) as its main active component, is recognized in traditional Chinese medicine (TCM) for its Qi-invigorating properties in the five visceral organs. Our laboratory ha...Schisandrae Fructus, containing schisandrin B (Sch B) as its main active component, is recognized in traditional Chinese medicine (TCM) for its Qi-invigorating properties in the five visceral organs. Our laboratory has shown that the Qi-invigorating action of Chinese tonifying herbs is linked to increased mitochondrial ATP generation and an enhancement in mitochondrial glutathione redox status. To explore whether Sch B can exert Qi-invigorating actions across various tissues, we investigated the effects of Sch B treatment on mitochondrial ATP generation and glutathione redox status in multiple mouse tissues ex vivo. In line with TCM theory, which posits that Zheng Qi generation relies on the Qi function of the visceral organs, we also examined Sch B’s impact on natural killer cell activity and antigen-induced splenocyte proliferation, both serving as indirect measures of Zheng Qi. Our findings revealed that Sch B treatment consistently enhanced mitochondrial ATP generation and improved mitochondrial glutathione redox status in mouse tissues. This boost in mitochondrial function was associated with stimulated innate and adaptive immune responses, marked by increased natural killer cell activity and antigen-induced T/B cell proliferation, potentially through the increased generation of Zheng Qi.展开更多
Alzheimer’s disease (AD) is the most common cause of dementia and is a growing public health challenge. Neuroinflammation has been proposed as a prominent pathological feature of AD and has traditionally been attribu...Alzheimer’s disease (AD) is the most common cause of dementia and is a growing public health challenge. Neuroinflammation has been proposed as a prominent pathological feature of AD and has traditionally been attributed to the innate immune system. However, emerging evidence highlights the involvement of adaptive immunity, particularly T and B lymphocytes, in the neuroinflammatory processes of AD. It remains unclear how adaptive immune responses, originally intended to protect the body, contribute to chronic inflammation and neuronal dysfunction in AD. Here, we review the roles of adaptive immunity, cellular composition, and niches and their contribution to AD development and progression. Notably, we synthesize the crosstalk between adaptive immunity and the innate immune system of the central nervous system (CNS), which is mainly mediated by glial cells and myeloid cells, and their interrelationships with amyloid-β (Aβ)/Tau pathology. We hypothesized that the alterations observed in innate immunity in AD mirror age-related immune alterations, whereas the dysregulation of adaptive immunity contributes more accurately to disease-specific immune responses. Targeting adaptive immunity in the context of neuroinflammation may provide new insights into potential therapeutic strategies designed to modulate immune responses, thereby facilitating the diagnosis, intervention, and treatment of AD.展开更多
In clinical practice,repairing osteochondral defects(OCDs)is challenging because of the complex cartilage/subchondral bone structure and intricate immunological microenvironment.Here,we identify the crucial role of ad...In clinical practice,repairing osteochondral defects(OCDs)is challenging because of the complex cartilage/subchondral bone structure and intricate immunological microenvironment.Here,we identify the crucial role of adaptive immunity dysfunction by revealing that an increase of T helper 17(Th17)cells exacerbated osteochondral tissue degradation via its pro-inflammatory cytokine interleukin-17(IL-17)in the early-stage OCDs.Next,we leveraged this adaptive immunity mechanism and combined it with regenerative signals to develop a multifunctional hydrogel system capable of simultaneously tackling immune dysfunction and regenerative deficiency.Rapid IL-4 release from the methacrylated hyaluronic acid(HAMA)hydrogel exerts a potent immunomodulatory effect by inhibiting the differentiation and function of Th17 cells.Moreover,transforming growth factor-beta1 anchored on methacrylated hyaluronic acid and heparin(HAMA@HepMA)microparticles provides sustained regenerative signals,which synergistically transform the pro-inflammatory microenvironment into a pro-regenerative niche for enhanced OCDs healing.Our study suggests that targeting specific immune pathways can significantly enhance the efficacy of regenerative strategies,paving the way for innovative treatments in orthopedic medicine.展开更多
The tumor suppressor phosphatase and tensin homolog(PTEN)is a lipid and protein phosphatase that is able to antagonize the PI3K/AKT pathway and inhibit tumor growth.PTEN also possesses phosphatase-independent function...The tumor suppressor phosphatase and tensin homolog(PTEN)is a lipid and protein phosphatase that is able to antagonize the PI3K/AKT pathway and inhibit tumor growth.PTEN also possesses phosphatase-independent functions.Genetic alterations of PTEN may lead to the deregulation of cell proliferation,survival,differentiation,energy metabolism and cellular architecture and mobility.Although the role of PTEN in tumor suppression is extensively documented and well established,the evidence for its roles in immunity did not start to accumulate until recently.In this review,we will focus on the newly discovered functions of PTEN in the regulation of innate and adaptive immunity,including antiviral responses.展开更多
Since its discovery in 1993, the mitogen-activated protein （MAP） kinase p38 has attracted much attention for its role in a wide range of cellular processes, many of which involve the immune system. Although p38 has ...Since its discovery in 1993, the mitogen-activated protein （MAP） kinase p38 has attracted much attention for its role in a wide range of cellular processes, many of which involve the immune system. Although p38 has been heavily implicated in the function of all type immune cells, research has tended focus on its role in innate immunity. In this review we attempt to highlight some of the major discoveries that have been made regarding p38＇s role in adaptive immunity, and also to discuss the possible future implications of these discoveries.展开更多
The anatomical architecture of the human liver and the diversity of its immune components endow the liver with its physiological function of immune competence. Adaptive immunity is a major arm of the immune system tha...The anatomical architecture of the human liver and the diversity of its immune components endow the liver with its physiological function of immune competence. Adaptive immunity is a major arm of the immune system that is organized in a highly specialized and systematic manner, thus providing long-lasting protection with immunological memory. Adaptive immunity consists of humoral immunity and cellular immunity. Cellular immunity is known to have a crucial role in controlling infection, cancer and autoimmune disorders in the liver. In this article, we will focus on hepatic virus infections, hepatocellular carcinoma and autoimmune disorders as examples to illustrate the current understanding of the contribution of T cells to cellular immunity in these maladies. Cellular immune suppression is primarily responsible for chronic viral infections and cancer. However, an uncontrolled auto-reactive immune response accounts for autoimmunity. Consequently, these immune abnormalities are ascribed to the quantitative and functional changes in adaptive immune cells and their subsets, innate immunocytes, chemokines, cytokines and various surface receptors on immune cells. A greater understanding of the complex orchestration of the hepatic adaptive immune regulators during homeostasis and immune competence are much needed to identify relevant targets for clinical intervention to treat immunological disorders in the liver.展开更多
Immunogenic dying tumor cells hold promising prospects as cancer vaccines to activate systemic immunity against both primary and metastatic tumors.Especially,X-ray-induced dying tumor cells are rich in highly immunoge...Immunogenic dying tumor cells hold promising prospects as cancer vaccines to activate systemic immunity against both primary and metastatic tumors.Especially,X-ray-induced dying tumor cells are rich in highly immunogenic tumor-associated antigens and self-generated dsDNA as potent adjuvants.However,we found that the X-ray induction process can result in the excessive exposure of phosphatidylserine in cancer vaccines,which can specifically bind with the MerTK receptor on macrophages,acting as a“checkpoint”to facilitate immune silence in the tumor microenvironment.Therefore,we developed a novel strategy combining X-ray-induced cancer vaccines with UNC2250,a macrophage MerTK“checkpoint inhibitor,”for treating peritoneal carcinomatosis in colon cancer.By incorporating UNC2250 into the treatment regimen,immunosuppressive efferocytosis of macrophages,which relies on MerTK-directed recognition of phosphatidylserine on vaccines,was effectively blocked.Consequently,the immune analysis revealed that this combination strategy promoted the maturation of dendritic cells and M1-like repolarization of macrophages,thereby simultaneously eliciting robust adaptive and innate immunity.This innovative approach utilizing X-ray-induced vaccines combined with a checkpoint inhibitor may provide valuable insights for developing effective cancer vaccines and immunotherapies targeting colon cancer.展开更多
Recent cumulative findings signify the adaptive immunity of materials as a key agenda in tissue healing that can improve regenerative events and outcomes. Modulating immune responses, mainly the recruitment and functi...Recent cumulative findings signify the adaptive immunity of materials as a key agenda in tissue healing that can improve regenerative events and outcomes. Modulating immune responses, mainly the recruitment and functions of T and B cells and their further interplay with innate immune cells (e.g., dendritic cells, macrophages) can be orchestrated by materials. For instance, decellularized matrices have been shown to promote muscle healing by inducing T helper 2 (Th2) cell immunity, while synthetic biopolymers exhibit differential effects on B cell responses and fibrosis compared decellularized matrices. We discuss the recent findings on how implantable materials instruct the adaptive immune events and the subsequent tissue healing process. In particular, we dissect the materials’ physicochemical properties (shape, size, topology, degradation, rigidity, and matrix dynamic mechanics) to demonstrate the relations of these parameters with the adaptive immune responses in vitro and the underlying biological mechanisms. Furthermore, we present evidence of recent in vivo phenomena, including tissue healing, cancer progression, and fibrosis, wherein biomaterials potentially shape adaptive immune cell functions and in vivo outcomes. Our discussion will help understand the materials-regulated immunology events more deeply, and offer the design rationale of materials with tunable matrix properties for accelerated tissue repair and regeneration.展开更多
Acute-on-chronic hepatitis B liver failure(ACHBLF)is a term used to define the acute deterioration of liver function that occurs in patients with chronic hepatitis B virus infection or hepatitis B virus-related liver ...Acute-on-chronic hepatitis B liver failure(ACHBLF)is a term used to define the acute deterioration of liver function that occurs in patients with chronic hepatitis B virus infection or hepatitis B virus-related liver cirrhosis.The specific pathogenesis of ACHBLF is still not completely understood.Current research has shown that an intense systemic inflammation is involved in the development of acute-on-chronic liver failure(ACLF).Meanwhile,a subsequent immune paresis over the course of ACLF favors the development of infection and sepsis.Deregulation in both the innate and adaptive immunity is the notable feature of ACLF.The dysregulated immune responses play a crucial role in disease progression and potentially drive organ failure and mortality in ACHBLF.In this review,we highlight the current knowledge of innate and adaptive immune cells in ACHBLF.展开更多
Microbes play a critical role in shaping immune development,with growing interest in how rhinovirus(RV)interacts with the host immune system,particularly in individuals with asthma and chronic obstructive pul-monary d...Microbes play a critical role in shaping immune development,with growing interest in how rhinovirus(RV)interacts with the host immune system,particularly in individuals with asthma and chronic obstructive pul-monary disease(COPD).Disruptions in microbial balance during RV infections can impair immune homeostasis and worsen disease outcomes.Recent studies emphasize RV-induced regulation of antiviral defenses,cytokine production,and immune tolerance.This review explores the interplay between RV,the immune system,and microbiota,highlighting the importance of these interactions in guiding effective therapies for respiratory in-fections.It advances existing literature by considering microbiota-mediated therapies as a novel approach to managing RV exacerbations in respiratory diseases like asthma and COPD.展开更多
In adaptive immunity,antigens are presented to T cells,which then become effector T cells(CD4+)or cytotoxic T cells(CD8+).These are called adaptive immune T cells.Cancer immunotherapy based on anti-programmed death re...In adaptive immunity,antigens are presented to T cells,which then become effector T cells(CD4+)or cytotoxic T cells(CD8+).These are called adaptive immune T cells.Cancer immunotherapy based on anti-programmed death receptor-1(PD-1)/programmed cell death 1 ligand 1(PD-L1)antibodies is a new way to treat cancer.Chinese herbal medicines are often used with cancer treatments in clinical practice.Recent studies have shown that Chinese herbal medicines affect the immune system and have an effect on PD-1/PD-L1.Baicalin,the main ingredient of Scutellaria baicalensis,can stop Tregs from working,increase the number of CD8+T cells in the tumour microenvironment and avoid PD-1 resistance.Solamargine has anti-cancer activity in a variety of tumours,including stopping tumour growth,stopping PD-L1 expression and blocking immune escape in combination with Immune checkpoint inhibitors.Taraxasterol,found in dandelion,can regulate anti-tumour T cells.It affects CD4+T cells by inhibiting STAT3.Platycodonis Radix can reduce the expression of PD-1 on the surface of CD8+T cells and increase their ability to kill tumour cells.Licorice compounds can regulate the cell cycle and PD-L1 expression,which can lead to tumour cell cycle blockade and increase the level of PD-L1 expression,thereby exerting anti-tumour effects.Marsdenia tenacissima extracts weakened the immunosuppressive effect of IL-10,improved T-cell function,stopped tumour cells escaping the immune system and reduced TGF-β1 and PD-L1.Strobilanthes crispus F3 extract increases lymphocyte infiltration,improves T-cell-mediated cytotoxicity,modulates immune cell expression,stops tumour-associated macrophage activity and slows tumour progression.The last five years of research on herbs with purgative and detoxifying effects were reviewed.This review will investigate how herbs can affect adaptive immune T cells in the immune system to improve cancer treatment.展开更多
Background:Dengue fever,an acute insect-borne infectious disease caused by the dengue virus(DENV),poses a great challenge to global public health.Hepatic involve-ment is the most common complication of severe dengue a...Background:Dengue fever,an acute insect-borne infectious disease caused by the dengue virus(DENV),poses a great challenge to global public health.Hepatic involve-ment is the most common complication of severe dengue and is closely related to the occurrence and development of disease.However,the features of adaptive immune responses associated with liver injury in severe dengue are not clear.Methods:We used single-cell sequencing to examine the liver tissues of mild or se-vere dengue mice model to analyze the changes in immune response of T cells in the liver after dengue virus infection,and the immune interaction between macrophages and T cells.Flow cytometry was used to detect T cells and macrophages in mouse liver and blood to verify the single-cell sequencing results.Results:Our result showed CTLs were significantly activated in the severe liver injury group but the immune function-related signal pathway was down-regulated.The rea-son may be that the excessive immune response in the severe group at the late stage of DENV infection induces the polarization of macrophages into M2 type,and the macrophages then inhibit T cell immunity through the TGF-βsignaling pathway.In ad-dition,the increased proportion of Treg cells suggested that Th17/Treg homeostasis was disrupted in the livers of severe liver injury mice.Conclusions:In this study,single-cell sequencing and flow cytometry revealed the characteristic changes of T cell immune response and the role of macrophages in the liver of severe dengue fever mice.Our study provides a better understanding of the pathogenesis of liver injury in dengue fever patients.展开更多
The complement system plays a crucial role in the innate defense against common pathogens. Activation of complement leads to robust and efficient proteolytic cascades, which terminate in opsonization and lysis of the ...The complement system plays a crucial role in the innate defense against common pathogens. Activation of complement leads to robust and efficient proteolytic cascades, which terminate in opsonization and lysis of the pathogen as well as in the generation of the classical inflammatory response through the production of potent proinflammatory molecules. More recently, however, the role of complement in the immune response has been expanded due to observations that link complement activation to adaptive immune responses. It is now appreciated that complement is a functional bridge between innate and adaptive immune responses that allows an integrated host defense to pathogenic challenges. As such, a study of its functions allows insight into the molecular underpinnings of host-pathogen interactions as well as the organization and orchestration of the host immune response. This review attempts to summarize the roles that complement plays in both innate and adaptive immune responses and the consequences of these interactions on host defense.展开更多
Inflammatory bowl disease （IBD） is a type 1 T helper cell （Th1）-mediated autoimmune disease. Various studies have revealed that environmental pathogens also play a significant role in the initiation and progressio...Inflammatory bowl disease （IBD） is a type 1 T helper cell （Th1）-mediated autoimmune disease. Various studies have revealed that environmental pathogens also play a significant role in the initiation and progression of this disease. Interestingly, the pathogenesis of IBD has been shown to be related to nitric oxide （NO） released from innate immune cells. Although NO is known to be highly toxic to the gut epithelia, there is very little information about the regulation of NO production, One major question in the etiology of IBD is how Thl cells and pathogens interact in the induction of IBD. In present study, we focused on the regulation of NO. We show that macrophages require both interferon-γ, （IFN-γ）-mediated and TLR4-mediated signals for the production of NO, which causes inflammation in the intestine and subsequently IBD. Thus, IBD is the result of concerted actions of innate immune signals, such as the binding of LPS to TLR-4, and adaptive immune signals, such as IFN-γ produced by Thl cells.展开更多
Chronic hepatitis B virus(HBV)infection is an international health problem with extremely high mortality and morbidity rates.Although current clinical chronic hepatitis B(CHB)treatment strategies can partly inhibit an...Chronic hepatitis B virus(HBV)infection is an international health problem with extremely high mortality and morbidity rates.Although current clinical chronic hepatitis B(CHB)treatment strategies can partly inhibit and eliminate HBV,viral breakthrough may result due to non-adherence to treatment,the emergence of viral resistance,and a long treatment cycle.Persistent CHB infection arises as a consequence of complex interactions between the virus and the host innate and adaptive immune systems.Therefore,understanding the immune escape mechanisms involved in persistent HBV infection is important for designing novel CHB treatment strategies to clear HBV and achieve long-lasting immune control.This review details the immunological and biological characteristics and escape mechanisms of HBV and the novel immune-based therapies that are currently used for treating HBV.展开更多
An overly exuberant immune response,characterized by a cytokine storm and uncontrolled inflammation,has been identified as a significant driver of severe coronavirus disease 2019(COVID-19)cases.Consequently,decipherin...An overly exuberant immune response,characterized by a cytokine storm and uncontrolled inflammation,has been identified as a significant driver of severe coronavirus disease 2019(COVID-19)cases.Consequently,deciphering the intricacies of immune dysregulation in COVID-19 is imperative to identify specific targets for intervention and modulation.With these delicate dynamics in mind,immunomodulatory therapies have emerged as a promising avenue for miti-gating the challenges posed by COVID-19.Precision in manipulating immune pathways presents an opportunity to alter the host response,optimizing antiviral defenses while curbing deleterious inflammation.This review article compre-hensively analyzes immunomodulatory interventions in managing COVID-19.We explore diverse approaches to mitigating the hyperactive immune response and its impact,from corticosteroids and non-steroidal drugs to targeted biologics,including anti-viral drugs,cytokine inhibitors,JAK inhibitors,convalescent plasma,monoclonal antibodies(mAbs)to severe acute respiratory syndrome coronavirus 2,cell-based therapies(i.e.,CAR T,etc.).By summarizing the current evidence,we aim to provide a clear roadmap for clinicians and researchers navigating the complex landscape of immunomodulation in COVID-19 treatment.CS Glucocorticoids are among the most widely prescribed drugs with their immune-suppressive and anti-inflammatory effect[84].The current guidelines for the treatment of COVID-19 recommend against the use of dexamethasone or other systemic CS in non-hospitalized patients in the absence of another indication[70].The RECOVERY trial demonstrates the reduced 28-d mortality among hospitalized patients with COVID-19 using dexamethasone compared to the usual standard of care,along with other investigators,such as Ahmed and Hassan[85].The benefit of dexamethasone was seen only among participants receiving either oxygen alone or invasive mechanical ventilation at randomization but not among those receiving no respiratory support at enrollment[85].In a systematic review and meta-analysis,Albuquerque et al[86]showed that in comparison to tocilizumab,baricitinib,and sarilumab are associated with high probabilities of similar mortality reductions among hospitalized COVID-19 concurrently treated with CS.As a result of the absence of SARS-CoV-2-specific antiviral medications,the effectiveness of COVID-19 treatments is reduced.Several COVID-19 therapies are now under investigation.However,the majority of them lack specificity,efficacy,and safety[87].Immunotherapy is a ground-breaking medical treatment that manipulates the immune system to fight diseases.Translational research is rapidly progressing,recognized as a significant breakthrough in 2013[88].Among the immunotherapeutic options for treating COVID-19 are Immunoglobulin,CP,antibodies,mAbs(mAbs),NK cells,T cells,TLR,cytokine therapies and immune modulators.展开更多
Innate immunity in fish is critically important for preventing the entry of pathogenic microorganisms by adeptly recognizing pathogen-associated molecular patterns(PAMPs)through pattern recognition receptors(PRRs).Con...Innate immunity in fish is critically important for preventing the entry of pathogenic microorganisms by adeptly recognizing pathogen-associated molecular patterns(PAMPs)through pattern recognition receptors(PRRs).Concurrently,the adaptive immune response equips the vertebrate immune system to identify and retain memory of specific pathogens,thereby facilitating enhanced secondary responses upon re-exposure.Antigen-presenting cells(APCs)are integral to this process,as they recognize antigens via mechanisms including PRRs,internalize them,and process these antigens for presentation to T cells.This interaction triggers the activation of both T cells and B cells,initiating a robust priming of the adaptive immune system and establishing a functional bridge between innate and adaptive immunity.Antigen presentation serves as a pivotal mechanism for T cell activation and B cell differentiation,thereby leading to the establishment of effective antimicrobial protection.Vaccination of fish is of paramount importance for preventing specific infectious diseases and is economically and environmentally essential for the development of a sustainable fish aquaculture industry.The design of efficacious vaccines necessitates the establishment of long-term protection against specific antigenic challenges,with APCs occupying a central role in this endeavor.This review summarizes the most recent studies on fish antigen presentation pathways and elucidates the mechanisms involved in the recognition,processing,and presentation of antigens by APCs,triggering activation of T cells.Moreover,this review highlights recent findings concerning immune regulatory factors that activate adaptive immunity,including adjuvants and immunostimulants,providing the prospects for fish vaccine applications.A comprehensive understanding of how fish APCs detect and respond to antigens will have profound implications for the future development of tailored vaccination strategies and the rational design of interventions against infectious diseases impacting the commercial aquaculture sector.展开更多
基金National Key R&D Program of China(2019YFA0110600)National Natural Science Foundation of China(81970916,81671031)the LU JIAXI International team program supported by the K.C.Wong Education Foundation and CAS and the Youth Innovation Promotion Association of CAS(Grant No.2016236).
文摘Obesity-induced insulin resistance is the hallmark of metabolic syndrome,and chronic,low-grade tissue inflammation links obesity to insulin resistance through the activation of tissue-infiltrating immune cells.Current therapeutic approaches lack efficacy and immunomodulatory capacity.Thus,a new therapeutic approach is needed to prevent chronic inflammation and alleviate insulin resistance.Here,we synthesized a tetrahedral framework nucleic acid(tFNA)nanoparticle that carried resveratrol(RSV)to inhibit tissue inflammation and improve insulin sensitivity in obese mice.The prepared nanoparticles,namely tFNAs-RSV,possessed the characteristics of simple synthesis,stable properties,good water solubility,and superior biocompatibility.The tFNA-based delivery ameliorated the lability of RSV and enhanced its therapeutic efficacy.In high-fat diet(HFD)-fed mice,the administration of tFNAs-RSV ameliorated insulin resistance by alleviating inflammation status.tFNAs-RSV could reverse M1 phenotype macrophages in tissues to M2 phenotype macrophages.As for adaptive immunity,the prepared nanoparticles could repress the activation of Th1 and Th17 and promote Th2 and Treg,leading to the alleviation of insulin resistance.Furthermore,this study is the first to demonstrate that tFNAs,a nucleic acid material,possess immunomodulatory capacity.Collectively,our findings demonstrate that tFNAs-RSV alleviate insulin resistance and ameliorate inflammation in HFD mice,suggesting that nucleic acid materials or nucleic acid-based delivery systems may be a potential agent for the treatment of insulin resistance and obesity-related metabolic diseases.
基金supported by the National Natural Science Foundation of China (No.50609028)
文摘Because of complexity and non-predictability of the tunnel surrounding rock, the problem with the determination of the physical and mechanical parameters of the surrounding rock has become a main obstacle to theoretical research and numerical analysis in tunnel engineering. During design, it is a frequent practice, therefore, to give recommended values by analog based on experience. It is a key point in current research to make use of the displacement back analytic method to comparatively accurately determine the parameters of the surrounding rock whereas artificial intelligence possesses an exceptionally strong capability of identifying, expressing and coping with such complex non-linear relationships. The parameters can be verified by searching the optimal network structure, using back analysis on measured data to search optimal parameters and performing direct computation of the obtained results. In the current paper, the direct analysis is performed with the biological emulation system and the software of Fast Lagrangian Analysis of Continua (FLAC3D. The high non-linearity, network reasoning and coupling ability of the neural network are employed. The output vector required of the training of the neural network is obtained with the numerical analysis software. And the overall space search is conducted by employing the Adaptive Immunity Algorithm. As a result, we are able to avoid the shortcoming that multiple parameters and optimized parameters are easy to fall into a local extremum. At the same time, the computing speed and efficiency are increased as well. Further, in the paper satisfactory conclusions are arrived at through the intelligent direct-back analysis on the monitored and measured data at the Erdaoya tunneling project. The results show that the physical and mechanical parameters obtained by the intelligent direct-back analysis proposed in the current paper have effectively improved the recommended values in the original prospecting data. This is of practical significance to the appraisal of stability and informationization design of the surrounding rock.
文摘The present study investigated the effect of treatment with methanolic extracts of Yin- and Yang-Chinese tonifying herbs on concanavalin A (Con A)/lipopolysaccharide (LPS)-stimulated splenocyte proliferation (adaptive immunity) and natural killer (NK) cell activity (innate immunity) in an ex vivo mouse model. The results indicated that while treatment with most Yin herbal extracts potentiated the Con A/LPS-stimulated splenocyte proliferation, only Yang (but not Yin) herbal extracts stimulated NK cell activity. The differential effects of Yin- and Yang-Chinese tonifying herbs on innate and adaptive immunity are consistent with the Chinese medicine theory which depicts the Yin and Yang functional components of Zheng Qi (vital energy), with the Yang component being responsible for the first line of defense against invading microorganisms (i.e., innate immunity) and the Yin oner serving as a follow-up defensive response (adaptive immunity).
文摘Schisandrae Fructus, containing schisandrin B (Sch B) as its main active component, is recognized in traditional Chinese medicine (TCM) for its Qi-invigorating properties in the five visceral organs. Our laboratory has shown that the Qi-invigorating action of Chinese tonifying herbs is linked to increased mitochondrial ATP generation and an enhancement in mitochondrial glutathione redox status. To explore whether Sch B can exert Qi-invigorating actions across various tissues, we investigated the effects of Sch B treatment on mitochondrial ATP generation and glutathione redox status in multiple mouse tissues ex vivo. In line with TCM theory, which posits that Zheng Qi generation relies on the Qi function of the visceral organs, we also examined Sch B’s impact on natural killer cell activity and antigen-induced splenocyte proliferation, both serving as indirect measures of Zheng Qi. Our findings revealed that Sch B treatment consistently enhanced mitochondrial ATP generation and improved mitochondrial glutathione redox status in mouse tissues. This boost in mitochondrial function was associated with stimulated innate and adaptive immune responses, marked by increased natural killer cell activity and antigen-induced T/B cell proliferation, potentially through the increased generation of Zheng Qi.
基金supported by grants from the National Science Foundation of China(Nos.U22A20298,82430041)National Science and Technology Innovation 2030 Major Projects(No.2022ZD0211603).
文摘Alzheimer’s disease (AD) is the most common cause of dementia and is a growing public health challenge. Neuroinflammation has been proposed as a prominent pathological feature of AD and has traditionally been attributed to the innate immune system. However, emerging evidence highlights the involvement of adaptive immunity, particularly T and B lymphocytes, in the neuroinflammatory processes of AD. It remains unclear how adaptive immune responses, originally intended to protect the body, contribute to chronic inflammation and neuronal dysfunction in AD. Here, we review the roles of adaptive immunity, cellular composition, and niches and their contribution to AD development and progression. Notably, we synthesize the crosstalk between adaptive immunity and the innate immune system of the central nervous system (CNS), which is mainly mediated by glial cells and myeloid cells, and their interrelationships with amyloid-β (Aβ)/Tau pathology. We hypothesized that the alterations observed in innate immunity in AD mirror age-related immune alterations, whereas the dysregulation of adaptive immunity contributes more accurately to disease-specific immune responses. Targeting adaptive immunity in the context of neuroinflammation may provide new insights into potential therapeutic strategies designed to modulate immune responses, thereby facilitating the diagnosis, intervention, and treatment of AD.
基金supported by National Natural Science Foundation of China(82071567,82101646,82102598,82172459 and 82102597)Natural Science Foundation of Zhejiang Province(LQ21H060008).
文摘In clinical practice,repairing osteochondral defects(OCDs)is challenging because of the complex cartilage/subchondral bone structure and intricate immunological microenvironment.Here,we identify the crucial role of adaptive immunity dysfunction by revealing that an increase of T helper 17(Th17)cells exacerbated osteochondral tissue degradation via its pro-inflammatory cytokine interleukin-17(IL-17)in the early-stage OCDs.Next,we leveraged this adaptive immunity mechanism and combined it with regenerative signals to develop a multifunctional hydrogel system capable of simultaneously tackling immune dysfunction and regenerative deficiency.Rapid IL-4 release from the methacrylated hyaluronic acid(HAMA)hydrogel exerts a potent immunomodulatory effect by inhibiting the differentiation and function of Th17 cells.Moreover,transforming growth factor-beta1 anchored on methacrylated hyaluronic acid and heparin(HAMA@HepMA)microparticles provides sustained regenerative signals,which synergistically transform the pro-inflammatory microenvironment into a pro-regenerative niche for enhanced OCDs healing.Our study suggests that targeting specific immune pathways can significantly enhance the efficacy of regenerative strategies,paving the way for innovative treatments in orthopedic medicine.
基金the financial support provided by the National Natural Science Foundation of China(81620108020 and 31300609)Hubei Province’s Outstanding Medical Academic Leader Program and Innovation Team(2015CFA009 to DG).
文摘The tumor suppressor phosphatase and tensin homolog(PTEN)is a lipid and protein phosphatase that is able to antagonize the PI3K/AKT pathway and inhibit tumor growth.PTEN also possesses phosphatase-independent functions.Genetic alterations of PTEN may lead to the deregulation of cell proliferation,survival,differentiation,energy metabolism and cellular architecture and mobility.Although the role of PTEN in tumor suppression is extensively documented and well established,the evidence for its roles in immunity did not start to accumulate until recently.In this review,we will focus on the newly discovered functions of PTEN in the regulation of innate and adaptive immunity,including antiviral responses.
文摘Since its discovery in 1993, the mitogen-activated protein （MAP） kinase p38 has attracted much attention for its role in a wide range of cellular processes, many of which involve the immune system. Although p38 has been heavily implicated in the function of all type immune cells, research has tended focus on its role in innate immunity. In this review we attempt to highlight some of the major discoveries that have been made regarding p38＇s role in adaptive immunity, and also to discuss the possible future implications of these discoveries.
文摘The anatomical architecture of the human liver and the diversity of its immune components endow the liver with its physiological function of immune competence. Adaptive immunity is a major arm of the immune system that is organized in a highly specialized and systematic manner, thus providing long-lasting protection with immunological memory. Adaptive immunity consists of humoral immunity and cellular immunity. Cellular immunity is known to have a crucial role in controlling infection, cancer and autoimmune disorders in the liver. In this article, we will focus on hepatic virus infections, hepatocellular carcinoma and autoimmune disorders as examples to illustrate the current understanding of the contribution of T cells to cellular immunity in these maladies. Cellular immune suppression is primarily responsible for chronic viral infections and cancer. However, an uncontrolled auto-reactive immune response accounts for autoimmunity. Consequently, these immune abnormalities are ascribed to the quantitative and functional changes in adaptive immune cells and their subsets, innate immunocytes, chemokines, cytokines and various surface receptors on immune cells. A greater understanding of the complex orchestration of the hepatic adaptive immune regulators during homeostasis and immune competence are much needed to identify relevant targets for clinical intervention to treat immunological disorders in the liver.
基金This research was supported by the National Natural Science Foundation of China(No.82104098,China)the Program for HUST Academic Frontier Youth Team(No.2018QYTD13,China)+1 种基金Wuhan Science and Technology Plan(2022023702025187,China)Natural Science Foundation of Hubei Province(2023AFD152,China).
文摘Immunogenic dying tumor cells hold promising prospects as cancer vaccines to activate systemic immunity against both primary and metastatic tumors.Especially,X-ray-induced dying tumor cells are rich in highly immunogenic tumor-associated antigens and self-generated dsDNA as potent adjuvants.However,we found that the X-ray induction process can result in the excessive exposure of phosphatidylserine in cancer vaccines,which can specifically bind with the MerTK receptor on macrophages,acting as a“checkpoint”to facilitate immune silence in the tumor microenvironment.Therefore,we developed a novel strategy combining X-ray-induced cancer vaccines with UNC2250,a macrophage MerTK“checkpoint inhibitor,”for treating peritoneal carcinomatosis in colon cancer.By incorporating UNC2250 into the treatment regimen,immunosuppressive efferocytosis of macrophages,which relies on MerTK-directed recognition of phosphatidylserine on vaccines,was effectively blocked.Consequently,the immune analysis revealed that this combination strategy promoted the maturation of dendritic cells and M1-like repolarization of macrophages,thereby simultaneously eliciting robust adaptive and innate immunity.This innovative approach utilizing X-ray-induced vaccines combined with a checkpoint inhibitor may provide valuable insights for developing effective cancer vaccines and immunotherapies targeting colon cancer.
基金National Research Foundation of Korea(NRF,2021R1A5A2022318,2019R1A6A1A11034536,RS-2023-00220408,RS-2024-00334160,RS-2024-00348908)Ministry of Science and ICT and Ministry of Education.
文摘Recent cumulative findings signify the adaptive immunity of materials as a key agenda in tissue healing that can improve regenerative events and outcomes. Modulating immune responses, mainly the recruitment and functions of T and B cells and their further interplay with innate immune cells (e.g., dendritic cells, macrophages) can be orchestrated by materials. For instance, decellularized matrices have been shown to promote muscle healing by inducing T helper 2 (Th2) cell immunity, while synthetic biopolymers exhibit differential effects on B cell responses and fibrosis compared decellularized matrices. We discuss the recent findings on how implantable materials instruct the adaptive immune events and the subsequent tissue healing process. In particular, we dissect the materials’ physicochemical properties (shape, size, topology, degradation, rigidity, and matrix dynamic mechanics) to demonstrate the relations of these parameters with the adaptive immune responses in vitro and the underlying biological mechanisms. Furthermore, we present evidence of recent in vivo phenomena, including tissue healing, cancer progression, and fibrosis, wherein biomaterials potentially shape adaptive immune cell functions and in vivo outcomes. Our discussion will help understand the materials-regulated immunology events more deeply, and offer the design rationale of materials with tunable matrix properties for accelerated tissue repair and regeneration.
基金This work was supported by the National Natural Science Foundation of China(No.81970522,No.82000564)Shandong University multidisciplinary research and innovation team of young scholars(2020QNQT11)+2 种基金Shandong Provincial Natural Science Foundation(ZR2019PH027)China Postdoctoral Science Foundation(2020M672074)the Young Taishan Scholars(tsqn202103169).
文摘Acute-on-chronic hepatitis B liver failure(ACHBLF)is a term used to define the acute deterioration of liver function that occurs in patients with chronic hepatitis B virus infection or hepatitis B virus-related liver cirrhosis.The specific pathogenesis of ACHBLF is still not completely understood.Current research has shown that an intense systemic inflammation is involved in the development of acute-on-chronic liver failure(ACLF).Meanwhile,a subsequent immune paresis over the course of ACLF favors the development of infection and sepsis.Deregulation in both the innate and adaptive immunity is the notable feature of ACLF.The dysregulated immune responses play a crucial role in disease progression and potentially drive organ failure and mortality in ACHBLF.In this review,we highlight the current knowledge of innate and adaptive immune cells in ACHBLF.
文摘Microbes play a critical role in shaping immune development,with growing interest in how rhinovirus(RV)interacts with the host immune system,particularly in individuals with asthma and chronic obstructive pul-monary disease(COPD).Disruptions in microbial balance during RV infections can impair immune homeostasis and worsen disease outcomes.Recent studies emphasize RV-induced regulation of antiviral defenses,cytokine production,and immune tolerance.This review explores the interplay between RV,the immune system,and microbiota,highlighting the importance of these interactions in guiding effective therapies for respiratory in-fections.It advances existing literature by considering microbiota-mediated therapies as a novel approach to managing RV exacerbations in respiratory diseases like asthma and COPD.
文摘In adaptive immunity,antigens are presented to T cells,which then become effector T cells(CD4+)or cytotoxic T cells(CD8+).These are called adaptive immune T cells.Cancer immunotherapy based on anti-programmed death receptor-1(PD-1)/programmed cell death 1 ligand 1(PD-L1)antibodies is a new way to treat cancer.Chinese herbal medicines are often used with cancer treatments in clinical practice.Recent studies have shown that Chinese herbal medicines affect the immune system and have an effect on PD-1/PD-L1.Baicalin,the main ingredient of Scutellaria baicalensis,can stop Tregs from working,increase the number of CD8+T cells in the tumour microenvironment and avoid PD-1 resistance.Solamargine has anti-cancer activity in a variety of tumours,including stopping tumour growth,stopping PD-L1 expression and blocking immune escape in combination with Immune checkpoint inhibitors.Taraxasterol,found in dandelion,can regulate anti-tumour T cells.It affects CD4+T cells by inhibiting STAT3.Platycodonis Radix can reduce the expression of PD-1 on the surface of CD8+T cells and increase their ability to kill tumour cells.Licorice compounds can regulate the cell cycle and PD-L1 expression,which can lead to tumour cell cycle blockade and increase the level of PD-L1 expression,thereby exerting anti-tumour effects.Marsdenia tenacissima extracts weakened the immunosuppressive effect of IL-10,improved T-cell function,stopped tumour cells escaping the immune system and reduced TGF-β1 and PD-L1.Strobilanthes crispus F3 extract increases lymphocyte infiltration,improves T-cell-mediated cytotoxicity,modulates immune cell expression,stops tumour-associated macrophage activity and slows tumour progression.The last five years of research on herbs with purgative and detoxifying effects were reviewed.This review will investigate how herbs can affect adaptive immune T cells in the immune system to improve cancer treatment.
基金Chinese Academy of Medical Sciences Initiative for Innovative Medicine,Grant/Award Number:2021-I2M-1-035 and 2022-I2M-1-011。
文摘Background:Dengue fever,an acute insect-borne infectious disease caused by the dengue virus(DENV),poses a great challenge to global public health.Hepatic involve-ment is the most common complication of severe dengue and is closely related to the occurrence and development of disease.However,the features of adaptive immune responses associated with liver injury in severe dengue are not clear.Methods:We used single-cell sequencing to examine the liver tissues of mild or se-vere dengue mice model to analyze the changes in immune response of T cells in the liver after dengue virus infection,and the immune interaction between macrophages and T cells.Flow cytometry was used to detect T cells and macrophages in mouse liver and blood to verify the single-cell sequencing results.Results:Our result showed CTLs were significantly activated in the severe liver injury group but the immune function-related signal pathway was down-regulated.The rea-son may be that the excessive immune response in the severe group at the late stage of DENV infection induces the polarization of macrophages into M2 type,and the macrophages then inhibit T cell immunity through the TGF-βsignaling pathway.In ad-dition,the increased proportion of Treg cells suggested that Th17/Treg homeostasis was disrupted in the livers of severe liver injury mice.Conclusions:In this study,single-cell sequencing and flow cytometry revealed the characteristic changes of T cell immune response and the role of macrophages in the liver of severe dengue fever mice.Our study provides a better understanding of the pathogenesis of liver injury in dengue fever patients.
文摘The complement system plays a crucial role in the innate defense against common pathogens. Activation of complement leads to robust and efficient proteolytic cascades, which terminate in opsonization and lysis of the pathogen as well as in the generation of the classical inflammatory response through the production of potent proinflammatory molecules. More recently, however, the role of complement in the immune response has been expanded due to observations that link complement activation to adaptive immune responses. It is now appreciated that complement is a functional bridge between innate and adaptive immune responses that allows an integrated host defense to pathogenic challenges. As such, a study of its functions allows insight into the molecular underpinnings of host-pathogen interactions as well as the organization and orchestration of the host immune response. This review attempts to summarize the roles that complement plays in both innate and adaptive immune responses and the consequences of these interactions on host defense.
文摘Inflammatory bowl disease （IBD） is a type 1 T helper cell （Th1）-mediated autoimmune disease. Various studies have revealed that environmental pathogens also play a significant role in the initiation and progression of this disease. Interestingly, the pathogenesis of IBD has been shown to be related to nitric oxide （NO） released from innate immune cells. Although NO is known to be highly toxic to the gut epithelia, there is very little information about the regulation of NO production, One major question in the etiology of IBD is how Thl cells and pathogens interact in the induction of IBD. In present study, we focused on the regulation of NO. We show that macrophages require both interferon-γ, （IFN-γ）-mediated and TLR4-mediated signals for the production of NO, which causes inflammation in the intestine and subsequently IBD. Thus, IBD is the result of concerted actions of innate immune signals, such as the binding of LPS to TLR-4, and adaptive immune signals, such as IFN-γ produced by Thl cells.
基金Supported by National Science Foundation for Young Scientists of China, No.82001687National Major Science and Technology Project for Control and Prevention of Major Infectious Diseases, No.2018ZX10301401+2 种基金National Postdoctoral Program for Innovative Talents, No.BX20190192China Postdoctoral Science Foundation, No.2020M672064National Basic Research Program of China, No.2013CB531503
文摘Chronic hepatitis B virus(HBV)infection is an international health problem with extremely high mortality and morbidity rates.Although current clinical chronic hepatitis B(CHB)treatment strategies can partly inhibit and eliminate HBV,viral breakthrough may result due to non-adherence to treatment,the emergence of viral resistance,and a long treatment cycle.Persistent CHB infection arises as a consequence of complex interactions between the virus and the host innate and adaptive immune systems.Therefore,understanding the immune escape mechanisms involved in persistent HBV infection is important for designing novel CHB treatment strategies to clear HBV and achieve long-lasting immune control.This review details the immunological and biological characteristics and escape mechanisms of HBV and the novel immune-based therapies that are currently used for treating HBV.
基金Supported by the European Union-Next Generation EU,through the National Recovery and Resilience Plan of the Republic of Bulgaria,No.BG-RRP-2.004-0008.
文摘An overly exuberant immune response,characterized by a cytokine storm and uncontrolled inflammation,has been identified as a significant driver of severe coronavirus disease 2019(COVID-19)cases.Consequently,deciphering the intricacies of immune dysregulation in COVID-19 is imperative to identify specific targets for intervention and modulation.With these delicate dynamics in mind,immunomodulatory therapies have emerged as a promising avenue for miti-gating the challenges posed by COVID-19.Precision in manipulating immune pathways presents an opportunity to alter the host response,optimizing antiviral defenses while curbing deleterious inflammation.This review article compre-hensively analyzes immunomodulatory interventions in managing COVID-19.We explore diverse approaches to mitigating the hyperactive immune response and its impact,from corticosteroids and non-steroidal drugs to targeted biologics,including anti-viral drugs,cytokine inhibitors,JAK inhibitors,convalescent plasma,monoclonal antibodies(mAbs)to severe acute respiratory syndrome coronavirus 2,cell-based therapies(i.e.,CAR T,etc.).By summarizing the current evidence,we aim to provide a clear roadmap for clinicians and researchers navigating the complex landscape of immunomodulation in COVID-19 treatment.CS Glucocorticoids are among the most widely prescribed drugs with their immune-suppressive and anti-inflammatory effect[84].The current guidelines for the treatment of COVID-19 recommend against the use of dexamethasone or other systemic CS in non-hospitalized patients in the absence of another indication[70].The RECOVERY trial demonstrates the reduced 28-d mortality among hospitalized patients with COVID-19 using dexamethasone compared to the usual standard of care,along with other investigators,such as Ahmed and Hassan[85].The benefit of dexamethasone was seen only among participants receiving either oxygen alone or invasive mechanical ventilation at randomization but not among those receiving no respiratory support at enrollment[85].In a systematic review and meta-analysis,Albuquerque et al[86]showed that in comparison to tocilizumab,baricitinib,and sarilumab are associated with high probabilities of similar mortality reductions among hospitalized COVID-19 concurrently treated with CS.As a result of the absence of SARS-CoV-2-specific antiviral medications,the effectiveness of COVID-19 treatments is reduced.Several COVID-19 therapies are now under investigation.However,the majority of them lack specificity,efficacy,and safety[87].Immunotherapy is a ground-breaking medical treatment that manipulates the immune system to fight diseases.Translational research is rapidly progressing,recognized as a significant breakthrough in 2013[88].Among the immunotherapeutic options for treating COVID-19 are Immunoglobulin,CP,antibodies,mAbs(mAbs),NK cells,T cells,TLR,cytokine therapies and immune modulators.
基金supported by the Regional Joint Fund of the National Natural Science Foundation of China(U23A20255)the National Natural Science Foundation of China(32102827 and 31972818)the Natural Science Foundation of Guangdong Province(2023A1515011697 and 2023A1515012201).
文摘Innate immunity in fish is critically important for preventing the entry of pathogenic microorganisms by adeptly recognizing pathogen-associated molecular patterns(PAMPs)through pattern recognition receptors(PRRs).Concurrently,the adaptive immune response equips the vertebrate immune system to identify and retain memory of specific pathogens,thereby facilitating enhanced secondary responses upon re-exposure.Antigen-presenting cells(APCs)are integral to this process,as they recognize antigens via mechanisms including PRRs,internalize them,and process these antigens for presentation to T cells.This interaction triggers the activation of both T cells and B cells,initiating a robust priming of the adaptive immune system and establishing a functional bridge between innate and adaptive immunity.Antigen presentation serves as a pivotal mechanism for T cell activation and B cell differentiation,thereby leading to the establishment of effective antimicrobial protection.Vaccination of fish is of paramount importance for preventing specific infectious diseases and is economically and environmentally essential for the development of a sustainable fish aquaculture industry.The design of efficacious vaccines necessitates the establishment of long-term protection against specific antigenic challenges,with APCs occupying a central role in this endeavor.This review summarizes the most recent studies on fish antigen presentation pathways and elucidates the mechanisms involved in the recognition,processing,and presentation of antigens by APCs,triggering activation of T cells.Moreover,this review highlights recent findings concerning immune regulatory factors that activate adaptive immunity,including adjuvants and immunostimulants,providing the prospects for fish vaccine applications.A comprehensive understanding of how fish APCs detect and respond to antigens will have profound implications for the future development of tailored vaccination strategies and the rational design of interventions against infectious diseases impacting the commercial aquaculture sector.
