OBJECTIVE:To explore the therapeutic effect and target of atractylenolide I(AT-I)on post-infectious irritable bowel syndrome(PI-IBS)rats.METHODS:Therefore,the preliminarily mechanism of AT-I in anti-PI-IBS were first ...OBJECTIVE:To explore the therapeutic effect and target of atractylenolide I(AT-I)on post-infectious irritable bowel syndrome(PI-IBS)rats.METHODS:Therefore,the preliminarily mechanism of AT-I in anti-PI-IBS were first predicted by network pharmacology and molecular docking,then the possible signaling pathways were systematically analyzed.Finally,the potential therapeutic targets and possible signaling pathways of AT-I on PI-IBS in Sprague-Dawley(SD)rat model were verified by experiments.RESULTS:AT-I could alleviate PI-IBS symptoms and reduce the expression of tumor necrosis factorα,interleukin-6 and Interferon-gamma in PI-IBS SD rat model and inhibit the c-Jun N-terminal kinase/inducible nitric oxide synthase(JNK/iNOS)pathway.Notably,AT-I treatment could inhibit the overexpression of polymeraseⅠand transcript release factor(PTRF).CONCLUSION:AT-I could alleviate PI-IBS symptoms through downregulation of PTRF and inhibiting the JNK/iNOS pathway.This study not only provides a scientific basis to clarify the anti-PI-IBS effect of AT-I and its mechanism but also suggests a novel promising therapeutic strategy to treat the PI-IBS.展开更多
Background:In patients with autoimmune hemolytic anemia(AIHA),the risk of relapse is high owing to persistent autoreactive B-cell activity.Multirefractory AIHA is a more advanced stage of disease that is defined by a ...Background:In patients with autoimmune hemolytic anemia(AIHA),the risk of relapse is high owing to persistent autoreactive B-cell activity.Multirefractory AIHA is a more advanced stage of disease that is defined by a lack of response to at least three lines of therapy.CD19-directed chimeric antigen receptor(CAR)T-cell therapy results in profound B-cell depletion and may be a useful approach to achieving drug-free remission in multirefractory AIHA.展开更多
The paradigm of cancer treatment has been reshaped by chimeric antigen receptor(CAR)αβT cell therapy,yet its full potential remains constrained by fundamental limitations.While conventional CARαβT cells have achie...The paradigm of cancer treatment has been reshaped by chimeric antigen receptor(CAR)αβT cell therapy,yet its full potential remains constrained by fundamental limitations.While conventional CARαβT cells have achieved notable success in hematological malignancies,their broader application is hindered by the high cost and delays of autologous manufacturing,as well as the critical risk of graft-vs-host disease(GvHD).In addition,their efficacy against solid tumors is often compromised by the immunosuppressive tumor microenvironment(TME).As a promising solution,γδT cells are being developed as an alternative CAR platform.Their intrinsic ability to recognize transformed cells in a major histocompatibility complex(MHC)-independent manner minimizes the risk of GvHD and supports the creation of safe,effective allogeneic therapies.Building on this unique biology,the therapeutic efficacy of CARγδT cells is being enhanced through advanced engineering strategies.Key innovations include“armoring”technologies,such as cytokine secretion,checkpoint blockade,and metabolic rewiring,to overcome local immunosuppression and improve persistence,as well as the use of induced pluripotent stem cells(iPSCs)to generate standardized products from a renewable and consistent source.This expanding technological toolbox is also enabling novel applications beyond oncology.For example,chimeric autoantibody receptor(CAAR)constructs built onγδT cells integrate both classical and emerging insights into CARγδT cell therapy,highlighting innovations that are driving the field toward safer,more versatile,and longer-lasting treatments for cancer and autoimmunity.In light of these advancements,this review provides an overview of the current understanding ofγδT cell biology and highlights emerging engineering strategies that enhance the efficacy and durability of CARγδT cells across oncologic and autoimmune contexts.展开更多
Parkinson's disease is a neurodegenerative disorder marked by the degeneration of dopaminergic neurons and clinical symptoms such as tremors,rigidity,and slowed movements.A key feature of Parkinson's disease i...Parkinson's disease is a neurodegenerative disorder marked by the degeneration of dopaminergic neurons and clinical symptoms such as tremors,rigidity,and slowed movements.A key feature of Parkinson's disease is the accumulation of misfoldedα-synuclein,forming insoluble Lewy bodies in the substantia nigra pars compacta,which contributes to neurodegeneration.Theseα-synuclein aggregates may act as autoantigens,leading to T-cell-mediated neuroinflammation and contributing to dopaminergic cell death.Our perspective explores the hypothesis that Parkinson's disease may have an autoimmune component,highlighting research that connects peripheral immune responses with neurodegeneration.T cells derived from Parkinson's disease patients appear to have the potential to initiate an autoimmune response againstα-synuclein and its modified peptides,possibly leading to the formation of neo-epitopes.Recent evidence associates Parkinson's disease with abnormal immune responses,as indicated by increased levels of immune cells,such as CD4^(+)and CD8^(+)T cells,observed in both patients and mouse models.The convergence of T cells filtration increasing major histocompatibility complex molecules,and the susceptibility of dopaminergic neurons supports the hypothesis that Parkinson's disease may exhibit autoimmune characteristics.Understanding the immune mechanisms involved in Parkinson's disease will be crucial for developing therapeutic strategies that target the autoimmune aspects of the disease.Novel approaches,including precision medicine based on major histocompatibility complex/human leukocyte antigen typing and early biomarker identification,could pave the way for immune-based treatments aimed at slowing or halting disease progression.This perspective explores the relationship between autoimmunity and Parkinson's disease,suggesting that further research could deepen understanding and offer new therapeutic avenues.In this paper,it is organized to provide a comprehensive perspective on the autoimmune aspects of Parkinson's disease.It investigates critical areas such as the autoimmune response observed in Parkinson's disease patients and the role of autoimmune mechanisms targetingα-synuclein in Parkinson's disease.The paper also examines the impact of CD4~+T cells,specifically Th1 and Th17,on neurons through in vitro and ex vivo studies.Additionally,it explores howα-synuclein influences glia-induced neuroinflammation in Parkinson's disease.The discussion extends to the clinical implications and therapeutic landscape,offering insights into potential treatments.Consequently,we aim to provide a comprehensive perspective on the autoimmune aspects of Parkinson's disease,incorporating both supportive and opposing views on its classification as an autoimmune disorder and exploring implications for clinical applications.展开更多
Objective Abnormal maternal thyroid function is associated with preterm birth.However,this association stays dubious in relevant individual studies for ethnic difference reasons and lack of direct supporting data.This...Objective Abnormal maternal thyroid function is associated with preterm birth.However,this association stays dubious in relevant individual studies for ethnic difference reasons and lack of direct supporting data.This study aimed to evaluate the relationship between preterm birth and thyroid dysfunction or autoimmunity based on ethnic differences.Methods Relevant studies were identified through searches of MEDLINE,Excerpta Medica,Wan Fang,China Biological Medicine disc,and China National Knowledge Infrastructure from inception to June 15,2016.Original articles in which an incidence or prevalence of thyroid dysfunction or autoimmunity before second trimester of pregnancy could be extracted were included.Results Thirty-two unique studies were included for the final meta-analysis.Patients involved were divided into two groups：Group 1（G1） and Group 2（G2） comprising of Asian and Caucasian populations,respectively.Positive thyroid antibodies were associated with the occurrence of preterm birth in both G1 [odds ratio（OR）：3.62,95% confidence interval（CI）：2.83-4.65] and G2（OR：1.35,95% CI：1.17-1.56）;hypothyroidism,only in G2（OR：1.20,CI：1.09-1.33）;and subclinical hypothyroidism or hypothyroxinemia,in neither group.Conclusion Thyroid autoimmunity may be a more favorable factor leading to preterm birth among pregnant women of different ethnicities,compared with thyroid dysfunction.展开更多
Immune-driven inflammation plays an important part inatherogenesis and is therefore believed to be key to thedevelopment of cardiovascular disease(CVD), whichis currently the leading cause of death in the Westernworld...Immune-driven inflammation plays an important part inatherogenesis and is therefore believed to be key to thedevelopment of cardiovascular disease(CVD), whichis currently the leading cause of death in the Westernworld. By fulfilling some of the Koch postulates, athero-genesis has even been proposed to be considered as anautoimmune disease, raising the hope that CVD couldbe prevented by immunomodulation. Nevertheless,the role of the immune system and autoimmune reac-tions in atherosclerosis appear to be a double edged-sword, with both pro-atherogenic and anti-atherogenicattributes. Hence, if immunomodulation is to becomea therapeutic option for atherosclerosis and CVD, it willbe crucial to correctly identify patients who might ben-efit from targeted suppression of deleterious autoim-mune responses. This could be achieved, for example, by the detection of disease-associated autoantibodies. In this work, we will review the currently available clini-cal, in vitro, and animal studies dedicated to autoan-tibodies against apolipoprotein A-1(anti-apoA-1 IgG), the major proteic fraction of high density lipoprotein. Current clinical studies indicate that high levels of anti-apoA-1 IgG are associated with a worse cardiovascular prognosis. In addition, in vitro and animal studies indi-cate a pro-inflammatory and pro-atherogenic role, sup-porting the hypothesis that these autoantibodies may play a direct causal role in CVD, and furthermore that they could potentially represent a therapeutic target for CVD in the future.展开更多
Irritable bowel syndrome(IBS)is a commonly encountered chronic functional gastrointestinal(GI)disorder.Approximately 10%of IBS patients can trace the onset of their symptoms to a previous a bout of infectious dysenter...Irritable bowel syndrome(IBS)is a commonly encountered chronic functional gastrointestinal(GI)disorder.Approximately 10%of IBS patients can trace the onset of their symptoms to a previous a bout of infectious dysentery.The appearance of new IBS symptoms following an infectious event is defined as post-infectiousIBS.Indeed,with the World Health Organization estimating between 2 and 4 billion cases annually,infectious diarrheal disease represents an incredible international healthcare burden.Additionally,compounding evidence suggests many commonly encountered enteropathogens as unique triggers behind IBS symptom generation and underlying pathophysiological features.A growing body of work provides evidence supporting a role for pathogen-mediated modifications in the resident intestinal microbiota,epithelial barrier integrity,effector cell functions,and innate and adaptive immune features,all proposed physiological manifestations that can underlie GI abnormalities in IBS.Enteric pathogens must employ a vast array of machinery to evade host protective immune mechanisms,and illicit successful infections.Consequently,the impact of infectious events on host physiology can be multidimensional in terms of anatomical location,functional scope,and duration.This review offers a unique discussion of the mechanisms employed by many commonly encountered enteric pathogens that cause acute disease,but may also lead to the establishment of chronic GI dysfunction compatible with IBS.展开更多
Inflammatory bowel disease(IBD) is characterized by chronic relapsing inflammatory disorders of the gastrointestinal tract, and includes two major phenotypes: ulcerative colitis and Crohn's disease. The pathogenes...Inflammatory bowel disease(IBD) is characterized by chronic relapsing inflammatory disorders of the gastrointestinal tract, and includes two major phenotypes: ulcerative colitis and Crohn's disease. The pathogenesis of IBD is not fully understood as of yet. It is believed that IBD results from complicated interactions between environmental factors, genetic predisposition, and immune disorders. mi RNAs are a class of small non-coding RNAs that can regulate gene expression by targeting the 3′-untranslated region of specific m RNAs for degradation or translational inhibition. mi RNAs are considered to play crucial regulatory roles in many biologic processes, such as immune cellular differentiation, proliferation, and apoptosis, and maintenance of immune homeostasis. Recently, aberrant expression of mi RNAs was revealed to play an important role in autoimmune diseases, including IBD. In this review, we discuss the current understanding of how mi RNAs regulate autoimmunity and inflammation by affecting the differentiation, maturation, and function of various immune cells. In particular, we focus on describing specific mi RNA expression profiles in tissues and peripheral blood that may be associated with the pathogenesis of IBD. In addition, we summarize the opportunities for utilizing mi RNAs as new biomarkers and as potential therapeutic targets in IBD.展开更多
The liver is the front line organ of the immune system.The liver contains the largest collection of phagocytic cells in the body that detect both pathogens that enter through the gut and endogenously produced antigens...The liver is the front line organ of the immune system.The liver contains the largest collection of phagocytic cells in the body that detect both pathogens that enter through the gut and endogenously produced antigens.This is possible by the highly developed differentiation capacity of the liver immune system between self-antigens or non-self-antigens,such as food antigens or pathogens.As an immune active organ,the liver functions as a gatekeeping barrier from the outside world,and it can create a rapid and strong immune response,under unfavorable conditions.However,the liver's assumed immune status is anti-inflammatory or immuno-tolerant.Dynamic interactions between the numerous populations of immune cells in the liver are key for maintaining the delicate balance between immune screening and immune tolerance.The anatomical structure of the liver can facilitate the preparation of lymphocytes,modulate the immune response against hepatotropic pathogens,and contribute to some of its unique immunological properties,particularly its capacity to induce antigen-specific tolerance.Since liver sinusoidal endothelial cell is fenestrated and lacks a basement membrane,circulating lymphocytes can closely contact with antigens,displayed by endothelial cells,Kupffer cells,and dendritic cells while passing through the sinusoids.Loss of immune tolerance,leading to an autoaggressive immune response in the liver,if not controlled,can lead to the induction of autoimmune or autoinflammatory diseases.This review mentions the unique features of liver immunity,and dysregulated immune responses in patients with autoimmune liver diseases who have a close association with inborn errors of immunity have also been the emphases.展开更多
AIM:To investigate the interstitial cells of Cajal(ICC) number using a new rat model.METHODS:Sprague-Dawley rats were assigned to two groups.The first group received gavage with Campylobacter jejuni(C.jejuni) 81-176.T...AIM:To investigate the interstitial cells of Cajal(ICC) number using a new rat model.METHODS:Sprague-Dawley rats were assigned to two groups.The first group received gavage with Campylobacter jejuni(C.jejuni) 81-176.The second group was gavaged with placebo.Three months after clearance of Campylobacter from the stool,precise segments of duodenum,jejunum,and ileum were ligated in self-contained loops of bowel that were preserved in anaerobic bags.Deep muscular plexus ICC(DMP-ICC) were quantified by two blinded readers assessing the tissue in a random,coded order.The number of ICC per villus was compared among controls,Campylobacter recovered rats without small intestinal bacterial overgrowth(SIBO),and Campylobacter recovered rats with SIBO.RESULTS:Three months after recovery,27% of rats gavaged with C.jejuni had SIBO.The rats with SIBO had a lower number of DMP-ICC than controls in the jejunum and ileum.Additionally there appeared to be a density threshold of 0.12 DMP-ICC/villus that was associated with SIBO.If ileal density of DMP-ICC was < 0.12 ICC/villus,54% of rats had SIBO compared to 9% among ileal sections with > 0.12(P<0.05).If the density of ICC was < 0.12 DMP-ICC/villus in more than one location of the bowel,88% of these had SIBO compared to 6% in those who did not(P<0.001).CONCLUSION:In this post-infectious rat model,the development of SIBO appears to be associated with a reduction in DMP-ICC.Further study of this rat model might help understand the pathophysiology of postinfectious irritable bowel syndrome.展开更多
An allelic variant of the protein tyrosin phosphatase non-receptor 22(PTPN22) gene, PTPN22 R620 W, constitutes the strongest non-HLA genetic risk factor for the development of type 1 diabetes(T1D). A numberstudies usi...An allelic variant of the protein tyrosin phosphatase non-receptor 22(PTPN22) gene, PTPN22 R620 W, constitutes the strongest non-HLA genetic risk factor for the development of type 1 diabetes(T1D). A numberstudies using mouse models have addressed how PTPN22 predisposes to T1D. PTPN22 downmodulation, overexpression or expression of the variant gene in genetically manipulated mice has generated controversial results. These discrepancies probably derive from the fact that PTPN22 has differential effects on innate and adaptive immune responses. Moreover, the effects of PTPN22 are dependent on other genetic variables. Here we discuss these findings and try to explain the discrepancies. Exploring the mechanism by which PTPN22 contributes to islet-specific autoimmunity could help us understand its role in T1D pathogenesis and exploit it as a potential therapeutic target to prevent the disease.展开更多
Sporadic cases of acute viral hepatitis E have been described in developed countries, despite the more common occurrence in endemic areas and developing countries. We present the case of a 58 years old Portuguese fema...Sporadic cases of acute viral hepatitis E have been described in developed countries, despite the more common occurrence in endemic areas and developing countries. We present the case of a 58 years old Portuguese female, with no epidemiological relevant factors, admitted with acute hepatitis with positive anti-nuclear antibodies, anti-smooth muscle antibody and high serum gamma globulin (> 1.5 fold increase). Serologies for hepatitis A virus, hepatitis B virus, hepatitis C virus, Epstein-Barr virus, cytomegalovirus, hereditary sensory neuropathy and varicella zoster virus were negative. Liver biopsy histology revealed changes compatible with autoimmune hepatitis. Prednisolone and azathioprine was started. She tested positive for immunoglobulin M anti hepatitis E virus (HEV) with detectable viremia by reverse transcription polymerase chain reaction (RT-PCR) technique. HEV-RNA was confirmed throughRT-PCR in a liver specimen, establishing the diagnosis of acute hepatitis E. Immunosuppression was stopped. She clinically improved, with resolution of laboratory abnormalities. Therefore, we confirmed acute hepatitis E as the diagnosis. We review the literature to elucidate about HEV infection and its autoimmune effects.展开更多
BACKGROUND Post-infectious irritable bowel syndrome(PI-IBS)is generally regarded as a functional disease.Several recent studies have reported the involvement of lowgrade inflammation and immunological dysfunction in P...BACKGROUND Post-infectious irritable bowel syndrome(PI-IBS)is generally regarded as a functional disease.Several recent studies have reported the involvement of lowgrade inflammation and immunological dysfunction in PI-IBS.T helper 17(Th17)polarization occurs in IBS.Adenosine and its receptors participate in intestinal inflammation and immune regulation.AIM To investigate the role of Th17 polarization of CD4+T cells regulated by adenosine 2A receptor(A2AR)in PI-IBS.METHODS A PI-IBS model was established by infecting mice with Trichinella spiralis.The intestinal A2AR and CD4+T lymphocytes were detected by immunohistochemistry,and the inflammatory cytokines were detected by enzyme-linked immunoassay.CD4+T lymphocytes present in the animal’s spleen were separated and cultured with or without A2AR agonist and antagonist.Western blotting and real-time quantitative polymerase chain reaction were performed to determine the effect of A2AR on the cells and intestinal tissue.Cytokine production was determined.The protein and mRNA levels of A2AR associated signaling pathway molecules were also evaluated.Furthermore,A2AR agonist and antagonist were injected into the mouse model and the clinical features were observed.RESULTS The PI-IBS mouse model showed increased expression of ATP and A2AR(P<0.05),and inhibition of A2AR improved the clinical features in PI-IBS,including the abdominal withdrawal reflex and colon transportation test(P<0.05).The number of intestinal CD4+T cells and interleukin-17(IL-17)protein levels increased during PI-IBS,which was reversed by administration of the A2AR antagonist(P<0.05).CD4+T cells expressed A2AR and produced IL-17 in vitro,which was regulated by the A2AR agonist and antagonist.The A2AR antagonist increased the production of IL-17 by CD4+T cells via the Janus kinase-signal transducer and activator of transcriptionreceptor-related orphan receptorγsignaling pathway.CONCLUSION The results of the present study suggested that the upregulation of A2AR increases PI-IBS by promoting the Th17 polarization of CD4+T cells.展开更多
AIM:To verify the prevalence of thyroid autoimmunity(TA) and the possible association between atopy and TA in children affected by skin disease.METHODS:Three hundred and twenty-four children consecutively referred due...AIM:To verify the prevalence of thyroid autoimmunity(TA) and the possible association between atopy and TA in children affected by skin disease.METHODS:Three hundred and twenty-four children consecutively referred due to skin disease symptoms to our Pediatric Department were enrolled.One hundred and eighty-seven were diagnosed with atopic dermatitis(AD),95 with acute urticaria,40 with chronic urticaria(CU),and 2 with alopecia areata(AA).According to the work-up for atopy,the children were divided into two groups:Atopics and non-atopics.TA was diagnosed by serum thyroid peroxidase autoantibodies and/or thyroglobulin autoantibodies levels more than twice normal values over a period of two months by immunoassay.RESULTS:In all children with skin disease,a significant prevalence of TA in atopies compared with non-atopies(13.67%vs 2.67%,P=0.0016) and a significant association between TA and atopy(OR=5.76,95%CI:1.71-19.35) were observed.These findings were confirmed as significant in children with AD:TA in atopies was 11.5%,while TA in non-atopies was2.7%(P=0.03,OR=4.68,95%CI:1.02-21.38).In addition,atopics with CU showed a significantly higher prevalence of TA(26.9%),but none of the non-atopics showed CU(P=0.0326).On the other hand,atopies with AA showed a 100%(2 out of 2) prevalence of TA,compared with none of the non-atopies.CONCLUSION:In children with skin disease,atopy seems to be associated with an increased risk of TA.展开更多
Increasing evidence shows that extremely low frequency electromagnetic fields（ELF-EMFs） stimulation is able to exert a certain action on autoimmunity and immune cells. In the past, the efficacy of pulsed ELFEMFs in ...Increasing evidence shows that extremely low frequency electromagnetic fields（ELF-EMFs） stimulation is able to exert a certain action on autoimmunity and immune cells. In the past, the efficacy of pulsed ELFEMFs in alleviating the symptoms and the progression of multiple sclerosis has been supported through their action on neurotransmission and on the autoimmune mechanisms responsible for demyelination. Regarding the immune system, ELF-EMF exposure contributes to a general activation of macrophages, resulting in changes of autoimmunity and several immunological reactions, such as increased reactive oxygen species-formation, enhanced phagocytic activity and increased production of chemokines. Transcranial electromagnetic brain stimulation is a non-invasive novel technique used recently to treat different neurodegenerative disorders, in particular Alzheimer＇s disease. Despite its proven value, the mechanisms through which EMF brain-stimulation exerts its beneficial action on neuronal function remains unclear. Recent studies have shown that its beneficial effects may be due to a neuroprotective effect on oxidative cell damage. On the basis of in vitro and clinical studies on brain activity, modulation by ELF-EMFs could possibly counteract the aberrant pro-inflammatory responses present in neurodegenerative disorders reducing their severity and their onset. The objective of this review is to provide a systematic overview of the published literature on EMFs and outline the most promising effects of ELF-EMFs in developing treatments of neurodegenerative disorders. In this regard, we review data supporting the role of ELF-EMF in generating immune-modulatory responses, neuromodulation, and potential neuroprotective benefits. Nonetheless, we reckon that the underlying mechanisms of interaction between EMF and the immune system are still to be completely understood and need further studies at a molecular level.展开更多
BACKGROUND Mesenchymal stem cells(MSCs)have been reported to possess immune regulatory effects in innate and adaptive immune reactions.MSCs can mediate intercellular communications by releasing extracellular vesicles(...BACKGROUND Mesenchymal stem cells(MSCs)have been reported to possess immune regulatory effects in innate and adaptive immune reactions.MSCs can mediate intercellular communications by releasing extracellular vesicles(EVs),which deliver functional molecules to targeted cells.MSC derived EVs(MSC-EVs)confer altering effects on many immune cells,including T lymphocytes,B lymphocytes,natural killer cells,dendritic cells,and macrophages.A large number of studies have suggested that MSC-EVs participate in regulating autoimmunity related diseases.This characteristic of MSC-EVs makes them be potential biomarkers for the diagnosis and treatment of autoimmunity related diseases.AIM To verify the potential of MSC-EVs for molecular targeted therapy of autoimmunity related diseases.METHODS Literature search was conducted in PubMed to retrieve the articles published between 2010 and 2020 in the English language.The keywords,such as“MSCs,”“EVs,”“exosome,”“autoimmunity,”“tumor immunity,”and“transplantation immunity,”and Boolean operator“AND”and“NOT”coalesced admirably to be used for searching studies on the specific molecular mechanisms of MSC-EVs in many immune cell types and many autoimmunity related diseases.Studies that did not investigate the molecular mechanisms of MSC-EVs in the occurrence and development of autoimmune diseases were excluded.RESULTS A total of 96 articles were chosen for final reference lists.After analyzing those publications,we found that it had been well documented that MSC-EVs have the ability to induce multiple immune cells,like T lymphocytes,B lymphocytes,natural killer cells,dendritic cells,and macrophages,to regulate immune responses in innate immunity and adaptive immunity.Many validated EVsdelivered molecules have been identified as key biomarkers,such as proteins,lipids,and nucleotides.Some EVs-encapsulated functional molecules can serve as promising therapeutic targets particularly for autoimmune disease.CONCLUSION MSC-EVs play an equally important part in the differentiation,activation,and proliferation of immune cells,and they may become potential biomarkers for diagnosis and treatment of autoimmunity related diseases.展开更多
Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection can give rise to different clinical manifestations that are directly related to viral tissue damage or indirectly induced by the antiviral immune re...Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection can give rise to different clinical manifestations that are directly related to viral tissue damage or indirectly induced by the antiviral immune response.Hyper-activation of the immune system in an attempt to eradicate the infection may trigger autoimmunity.Several immune-mediated disorders have been described in SARS-CoV-2-infected individuals.These include cutaneous rashes and vasculitis,autoimmune cytopenia,anti-phospholipid syndrome,central or peripheral neuropathy,myositis and myocarditis.On the other hand,rheumatic patients were reported to have similar coronavirus disease 2019(COVID-19)incidence,morbidity and mortality rates compared to general population.This opinion review will summarize the crucial immunologic steps which occur during SARSCoV-2-infection that may link autoimmunity to COVID-19 and provides an opportunity for further discussion regarding this association.展开更多
Primary biliary cirrhosis(PBC) is an autoimmune liver disease characterized by the presence of serum autoantibodies and chronic nonsuppurative destructive cholangitis.The pathogenesis of PBC involves environmental fac...Primary biliary cirrhosis(PBC) is an autoimmune liver disease characterized by the presence of serum autoantibodies and chronic nonsuppurative destructive cholangitis.The pathogenesis of PBC involves environmental factors,genetic predisposition and loss of immune tolerance.In recent years,it has become univocally accepted that an inappropriately activated immune response is one of the most important factors in PBC.In this study,the role of autoimmunity in PBC is summarized and a feasible research orientation is recommended.展开更多
Genomic disruption of Fyn has not been associated with an immune-deficient phenotype, notwithstanding the profound impairment in IL-2 production by T cells derived from Fyn-deficient animals observed in vitro. The res...Genomic disruption of Fyn has not been associated with an immune-deficient phenotype, notwithstanding the profound impairment in IL-2 production by T cells derived from Fyn-deficient animals observed in vitro. The results presented demonstrate that Fyn deficient animals succumb to influenza infection ahead of the protective expansion of lung infiltrating T cells and viral clearance observed in wild-type hosts. Formal proof that Fyn-dependent IL-2 production mediates T cell expansion in vivo is provided using a model of T cell induced enteropathy. Specifically, Fyn deficient naive T cells do not induce colitis in SCID animals due to their lack of expansion, and Fyn re-expression rescues both IL-2 production and its capacity to support in vivo expansion leading to colitis. These results reconcile the obligatory role of Fyn in T cell activation and autocrine IL-2 supported growth;and underscore the mechanism through which its function is integrated with and regulated by Lck.展开更多
基金The University Collaborative Innovation Project of Anhui:Creation of a Combined Animal Model of Coronary Heart Disease based on the Theory of Xin'an Medicine(No.GXXT-2020-024)Start-up Funding for Doctoral Research at Wannan Medical College(WYRCQD2018009)Horizontal Project of South Anhui Medical College(H202003)。
文摘OBJECTIVE:To explore the therapeutic effect and target of atractylenolide I(AT-I)on post-infectious irritable bowel syndrome(PI-IBS)rats.METHODS:Therefore,the preliminarily mechanism of AT-I in anti-PI-IBS were first predicted by network pharmacology and molecular docking,then the possible signaling pathways were systematically analyzed.Finally,the potential therapeutic targets and possible signaling pathways of AT-I on PI-IBS in Sprague-Dawley(SD)rat model were verified by experiments.RESULTS:AT-I could alleviate PI-IBS symptoms and reduce the expression of tumor necrosis factorα,interleukin-6 and Interferon-gamma in PI-IBS SD rat model and inhibit the c-Jun N-terminal kinase/inducible nitric oxide synthase(JNK/iNOS)pathway.Notably,AT-I treatment could inhibit the overexpression of polymeraseⅠand transcript release factor(PTRF).CONCLUSION:AT-I could alleviate PI-IBS symptoms through downregulation of PTRF and inhibiting the JNK/iNOS pathway.This study not only provides a scientific basis to clarify the anti-PI-IBS effect of AT-I and its mechanism but also suggests a novel promising therapeutic strategy to treat the PI-IBS.
文摘Background:In patients with autoimmune hemolytic anemia(AIHA),the risk of relapse is high owing to persistent autoreactive B-cell activity.Multirefractory AIHA is a more advanced stage of disease that is defined by a lack of response to at least three lines of therapy.CD19-directed chimeric antigen receptor(CAR)T-cell therapy results in profound B-cell depletion and may be a useful approach to achieving drug-free remission in multirefractory AIHA.
基金supported by the National Research Foundation of Korea(NRF)through the Ministry of Education(2021R1I1A3059820)(to Jea-Hyun Baek).
文摘The paradigm of cancer treatment has been reshaped by chimeric antigen receptor(CAR)αβT cell therapy,yet its full potential remains constrained by fundamental limitations.While conventional CARαβT cells have achieved notable success in hematological malignancies,their broader application is hindered by the high cost and delays of autologous manufacturing,as well as the critical risk of graft-vs-host disease(GvHD).In addition,their efficacy against solid tumors is often compromised by the immunosuppressive tumor microenvironment(TME).As a promising solution,γδT cells are being developed as an alternative CAR platform.Their intrinsic ability to recognize transformed cells in a major histocompatibility complex(MHC)-independent manner minimizes the risk of GvHD and supports the creation of safe,effective allogeneic therapies.Building on this unique biology,the therapeutic efficacy of CARγδT cells is being enhanced through advanced engineering strategies.Key innovations include“armoring”technologies,such as cytokine secretion,checkpoint blockade,and metabolic rewiring,to overcome local immunosuppression and improve persistence,as well as the use of induced pluripotent stem cells(iPSCs)to generate standardized products from a renewable and consistent source.This expanding technological toolbox is also enabling novel applications beyond oncology.For example,chimeric autoantibody receptor(CAAR)constructs built onγδT cells integrate both classical and emerging insights into CARγδT cell therapy,highlighting innovations that are driving the field toward safer,more versatile,and longer-lasting treatments for cancer and autoimmunity.In light of these advancements,this review provides an overview of the current understanding ofγδT cell biology and highlights emerging engineering strategies that enhance the efficacy and durability of CARγδT cells across oncologic and autoimmune contexts.
基金supported by the National Research Foundation of South Korea(2023R1A2C2004516,RS-2023-00219399 to SPY,and 2022R1I1A1A01063513 to MGJ)。
文摘Parkinson's disease is a neurodegenerative disorder marked by the degeneration of dopaminergic neurons and clinical symptoms such as tremors,rigidity,and slowed movements.A key feature of Parkinson's disease is the accumulation of misfoldedα-synuclein,forming insoluble Lewy bodies in the substantia nigra pars compacta,which contributes to neurodegeneration.Theseα-synuclein aggregates may act as autoantigens,leading to T-cell-mediated neuroinflammation and contributing to dopaminergic cell death.Our perspective explores the hypothesis that Parkinson's disease may have an autoimmune component,highlighting research that connects peripheral immune responses with neurodegeneration.T cells derived from Parkinson's disease patients appear to have the potential to initiate an autoimmune response againstα-synuclein and its modified peptides,possibly leading to the formation of neo-epitopes.Recent evidence associates Parkinson's disease with abnormal immune responses,as indicated by increased levels of immune cells,such as CD4^(+)and CD8^(+)T cells,observed in both patients and mouse models.The convergence of T cells filtration increasing major histocompatibility complex molecules,and the susceptibility of dopaminergic neurons supports the hypothesis that Parkinson's disease may exhibit autoimmune characteristics.Understanding the immune mechanisms involved in Parkinson's disease will be crucial for developing therapeutic strategies that target the autoimmune aspects of the disease.Novel approaches,including precision medicine based on major histocompatibility complex/human leukocyte antigen typing and early biomarker identification,could pave the way for immune-based treatments aimed at slowing or halting disease progression.This perspective explores the relationship between autoimmunity and Parkinson's disease,suggesting that further research could deepen understanding and offer new therapeutic avenues.In this paper,it is organized to provide a comprehensive perspective on the autoimmune aspects of Parkinson's disease.It investigates critical areas such as the autoimmune response observed in Parkinson's disease patients and the role of autoimmune mechanisms targetingα-synuclein in Parkinson's disease.The paper also examines the impact of CD4~+T cells,specifically Th1 and Th17,on neurons through in vitro and ex vivo studies.Additionally,it explores howα-synuclein influences glia-induced neuroinflammation in Parkinson's disease.The discussion extends to the clinical implications and therapeutic landscape,offering insights into potential treatments.Consequently,we aim to provide a comprehensive perspective on the autoimmune aspects of Parkinson's disease,incorporating both supportive and opposing views on its classification as an autoimmune disorder and exploring implications for clinical applications.
基金funded by the National Natural Science Foundation of China(Grant No.81302277)
文摘Objective Abnormal maternal thyroid function is associated with preterm birth.However,this association stays dubious in relevant individual studies for ethnic difference reasons and lack of direct supporting data.This study aimed to evaluate the relationship between preterm birth and thyroid dysfunction or autoimmunity based on ethnic differences.Methods Relevant studies were identified through searches of MEDLINE,Excerpta Medica,Wan Fang,China Biological Medicine disc,and China National Knowledge Infrastructure from inception to June 15,2016.Original articles in which an incidence or prevalence of thyroid dysfunction or autoimmunity before second trimester of pregnancy could be extracted were included.Results Thirty-two unique studies were included for the final meta-analysis.Patients involved were divided into two groups：Group 1（G1） and Group 2（G2） comprising of Asian and Caucasian populations,respectively.Positive thyroid antibodies were associated with the occurrence of preterm birth in both G1 [odds ratio（OR）：3.62,95% confidence interval（CI）：2.83-4.65] and G2（OR：1.35,95% CI：1.17-1.56）;hypothyroidism,only in G2（OR：1.20,CI：1.09-1.33）;and subclinical hypothyroidism or hypothyroxinemia,in neither group.Conclusion Thyroid autoimmunity may be a more favorable factor leading to preterm birth among pregnant women of different ethnicities,compared with thyroid dysfunction.
基金Supported by Swiss National Science Foundation Grants to Dr.Vuilleumier N No.310030_140736and to Dr.Montecucco F No.32003B_134963/1a grant from the Foundation"Gustave and Simone Prévot"to Dr.Montecucco F
文摘Immune-driven inflammation plays an important part inatherogenesis and is therefore believed to be key to thedevelopment of cardiovascular disease(CVD), whichis currently the leading cause of death in the Westernworld. By fulfilling some of the Koch postulates, athero-genesis has even been proposed to be considered as anautoimmune disease, raising the hope that CVD couldbe prevented by immunomodulation. Nevertheless,the role of the immune system and autoimmune reac-tions in atherosclerosis appear to be a double edged-sword, with both pro-atherogenic and anti-atherogenicattributes. Hence, if immunomodulation is to becomea therapeutic option for atherosclerosis and CVD, it willbe crucial to correctly identify patients who might ben-efit from targeted suppression of deleterious autoim-mune responses. This could be achieved, for example, by the detection of disease-associated autoantibodies. In this work, we will review the currently available clini-cal, in vitro, and animal studies dedicated to autoan-tibodies against apolipoprotein A-1(anti-apoA-1 IgG), the major proteic fraction of high density lipoprotein. Current clinical studies indicate that high levels of anti-apoA-1 IgG are associated with a worse cardiovascular prognosis. In addition, in vitro and animal studies indi-cate a pro-inflammatory and pro-atherogenic role, sup-porting the hypothesis that these autoantibodies may play a direct causal role in CVD, and furthermore that they could potentially represent a therapeutic target for CVD in the future.
基金Supported by Natural Sciences and Engineering Research Council of Canada(individual operating and CREATE)
文摘Irritable bowel syndrome(IBS)is a commonly encountered chronic functional gastrointestinal(GI)disorder.Approximately 10%of IBS patients can trace the onset of their symptoms to a previous a bout of infectious dysentery.The appearance of new IBS symptoms following an infectious event is defined as post-infectiousIBS.Indeed,with the World Health Organization estimating between 2 and 4 billion cases annually,infectious diarrheal disease represents an incredible international healthcare burden.Additionally,compounding evidence suggests many commonly encountered enteropathogens as unique triggers behind IBS symptom generation and underlying pathophysiological features.A growing body of work provides evidence supporting a role for pathogen-mediated modifications in the resident intestinal microbiota,epithelial barrier integrity,effector cell functions,and innate and adaptive immune features,all proposed physiological manifestations that can underlie GI abnormalities in IBS.Enteric pathogens must employ a vast array of machinery to evade host protective immune mechanisms,and illicit successful infections.Consequently,the impact of infectious events on host physiology can be multidimensional in terms of anatomical location,functional scope,and duration.This review offers a unique discussion of the mechanisms employed by many commonly encountered enteric pathogens that cause acute disease,but may also lead to the establishment of chronic GI dysfunction compatible with IBS.
基金the National Natural Science Foundation of China,No.81270469
文摘Inflammatory bowel disease(IBD) is characterized by chronic relapsing inflammatory disorders of the gastrointestinal tract, and includes two major phenotypes: ulcerative colitis and Crohn's disease. The pathogenesis of IBD is not fully understood as of yet. It is believed that IBD results from complicated interactions between environmental factors, genetic predisposition, and immune disorders. mi RNAs are a class of small non-coding RNAs that can regulate gene expression by targeting the 3′-untranslated region of specific m RNAs for degradation or translational inhibition. mi RNAs are considered to play crucial regulatory roles in many biologic processes, such as immune cellular differentiation, proliferation, and apoptosis, and maintenance of immune homeostasis. Recently, aberrant expression of mi RNAs was revealed to play an important role in autoimmune diseases, including IBD. In this review, we discuss the current understanding of how mi RNAs regulate autoimmunity and inflammation by affecting the differentiation, maturation, and function of various immune cells. In particular, we focus on describing specific mi RNA expression profiles in tissues and peripheral blood that may be associated with the pathogenesis of IBD. In addition, we summarize the opportunities for utilizing mi RNAs as new biomarkers and as potential therapeutic targets in IBD.
文摘The liver is the front line organ of the immune system.The liver contains the largest collection of phagocytic cells in the body that detect both pathogens that enter through the gut and endogenously produced antigens.This is possible by the highly developed differentiation capacity of the liver immune system between self-antigens or non-self-antigens,such as food antigens or pathogens.As an immune active organ,the liver functions as a gatekeeping barrier from the outside world,and it can create a rapid and strong immune response,under unfavorable conditions.However,the liver's assumed immune status is anti-inflammatory or immuno-tolerant.Dynamic interactions between the numerous populations of immune cells in the liver are key for maintaining the delicate balance between immune screening and immune tolerance.The anatomical structure of the liver can facilitate the preparation of lymphocytes,modulate the immune response against hepatotropic pathogens,and contribute to some of its unique immunological properties,particularly its capacity to induce antigen-specific tolerance.Since liver sinusoidal endothelial cell is fenestrated and lacks a basement membrane,circulating lymphocytes can closely contact with antigens,displayed by endothelial cells,Kupffer cells,and dendritic cells while passing through the sinusoids.Loss of immune tolerance,leading to an autoaggressive immune response in the liver,if not controlled,can lead to the induction of autoimmune or autoinflammatory diseases.This review mentions the unique features of liver immunity,and dysregulated immune responses in patients with autoimmune liver diseases who have a close association with inborn errors of immunity have also been the emphases.
基金Supported by A grant from Beatrice and Samuel A Seaver Foundation as well as the Shoolman Foundation
文摘AIM:To investigate the interstitial cells of Cajal(ICC) number using a new rat model.METHODS:Sprague-Dawley rats were assigned to two groups.The first group received gavage with Campylobacter jejuni(C.jejuni) 81-176.The second group was gavaged with placebo.Three months after clearance of Campylobacter from the stool,precise segments of duodenum,jejunum,and ileum were ligated in self-contained loops of bowel that were preserved in anaerobic bags.Deep muscular plexus ICC(DMP-ICC) were quantified by two blinded readers assessing the tissue in a random,coded order.The number of ICC per villus was compared among controls,Campylobacter recovered rats without small intestinal bacterial overgrowth(SIBO),and Campylobacter recovered rats with SIBO.RESULTS:Three months after recovery,27% of rats gavaged with C.jejuni had SIBO.The rats with SIBO had a lower number of DMP-ICC than controls in the jejunum and ileum.Additionally there appeared to be a density threshold of 0.12 DMP-ICC/villus that was associated with SIBO.If ileal density of DMP-ICC was < 0.12 ICC/villus,54% of rats had SIBO compared to 9% among ileal sections with > 0.12(P<0.05).If the density of ICC was < 0.12 DMP-ICC/villus in more than one location of the bowel,88% of these had SIBO compared to 6% in those who did not(P<0.001).CONCLUSION:In this post-infectious rat model,the development of SIBO appears to be associated with a reduction in DMP-ICC.Further study of this rat model might help understand the pathophysiology of postinfectious irritable bowel syndrome.
文摘An allelic variant of the protein tyrosin phosphatase non-receptor 22(PTPN22) gene, PTPN22 R620 W, constitutes the strongest non-HLA genetic risk factor for the development of type 1 diabetes(T1D). A numberstudies using mouse models have addressed how PTPN22 predisposes to T1D. PTPN22 downmodulation, overexpression or expression of the variant gene in genetically manipulated mice has generated controversial results. These discrepancies probably derive from the fact that PTPN22 has differential effects on innate and adaptive immune responses. Moreover, the effects of PTPN22 are dependent on other genetic variables. Here we discuss these findings and try to explain the discrepancies. Exploring the mechanism by which PTPN22 contributes to islet-specific autoimmunity could help us understand its role in T1D pathogenesis and exploit it as a potential therapeutic target to prevent the disease.
文摘Sporadic cases of acute viral hepatitis E have been described in developed countries, despite the more common occurrence in endemic areas and developing countries. We present the case of a 58 years old Portuguese female, with no epidemiological relevant factors, admitted with acute hepatitis with positive anti-nuclear antibodies, anti-smooth muscle antibody and high serum gamma globulin (> 1.5 fold increase). Serologies for hepatitis A virus, hepatitis B virus, hepatitis C virus, Epstein-Barr virus, cytomegalovirus, hereditary sensory neuropathy and varicella zoster virus were negative. Liver biopsy histology revealed changes compatible with autoimmune hepatitis. Prednisolone and azathioprine was started. She tested positive for immunoglobulin M anti hepatitis E virus (HEV) with detectable viremia by reverse transcription polymerase chain reaction (RT-PCR) technique. HEV-RNA was confirmed throughRT-PCR in a liver specimen, establishing the diagnosis of acute hepatitis E. Immunosuppression was stopped. She clinically improved, with resolution of laboratory abnormalities. Therefore, we confirmed acute hepatitis E as the diagnosis. We review the literature to elucidate about HEV infection and its autoimmune effects.
基金Supported by National Natural Science Foundation of China,No.81160057,No.81860102,and No.82060102.
文摘BACKGROUND Post-infectious irritable bowel syndrome(PI-IBS)is generally regarded as a functional disease.Several recent studies have reported the involvement of lowgrade inflammation and immunological dysfunction in PI-IBS.T helper 17(Th17)polarization occurs in IBS.Adenosine and its receptors participate in intestinal inflammation and immune regulation.AIM To investigate the role of Th17 polarization of CD4+T cells regulated by adenosine 2A receptor(A2AR)in PI-IBS.METHODS A PI-IBS model was established by infecting mice with Trichinella spiralis.The intestinal A2AR and CD4+T lymphocytes were detected by immunohistochemistry,and the inflammatory cytokines were detected by enzyme-linked immunoassay.CD4+T lymphocytes present in the animal’s spleen were separated and cultured with or without A2AR agonist and antagonist.Western blotting and real-time quantitative polymerase chain reaction were performed to determine the effect of A2AR on the cells and intestinal tissue.Cytokine production was determined.The protein and mRNA levels of A2AR associated signaling pathway molecules were also evaluated.Furthermore,A2AR agonist and antagonist were injected into the mouse model and the clinical features were observed.RESULTS The PI-IBS mouse model showed increased expression of ATP and A2AR(P<0.05),and inhibition of A2AR improved the clinical features in PI-IBS,including the abdominal withdrawal reflex and colon transportation test(P<0.05).The number of intestinal CD4+T cells and interleukin-17(IL-17)protein levels increased during PI-IBS,which was reversed by administration of the A2AR antagonist(P<0.05).CD4+T cells expressed A2AR and produced IL-17 in vitro,which was regulated by the A2AR agonist and antagonist.The A2AR antagonist increased the production of IL-17 by CD4+T cells via the Janus kinase-signal transducer and activator of transcriptionreceptor-related orphan receptorγsignaling pathway.CONCLUSION The results of the present study suggested that the upregulation of A2AR increases PI-IBS by promoting the Th17 polarization of CD4+T cells.
文摘AIM:To verify the prevalence of thyroid autoimmunity(TA) and the possible association between atopy and TA in children affected by skin disease.METHODS:Three hundred and twenty-four children consecutively referred due to skin disease symptoms to our Pediatric Department were enrolled.One hundred and eighty-seven were diagnosed with atopic dermatitis(AD),95 with acute urticaria,40 with chronic urticaria(CU),and 2 with alopecia areata(AA).According to the work-up for atopy,the children were divided into two groups:Atopics and non-atopics.TA was diagnosed by serum thyroid peroxidase autoantibodies and/or thyroglobulin autoantibodies levels more than twice normal values over a period of two months by immunoassay.RESULTS:In all children with skin disease,a significant prevalence of TA in atopies compared with non-atopies(13.67%vs 2.67%,P=0.0016) and a significant association between TA and atopy(OR=5.76,95%CI:1.71-19.35) were observed.These findings were confirmed as significant in children with AD:TA in atopies was 11.5%,while TA in non-atopies was2.7%(P=0.03,OR=4.68,95%CI:1.02-21.38).In addition,atopics with CU showed a significantly higher prevalence of TA(26.9%),but none of the non-atopics showed CU(P=0.0326).On the other hand,atopies with AA showed a 100%(2 out of 2) prevalence of TA,compared with none of the non-atopies.CONCLUSION:In children with skin disease,atopy seems to be associated with an increased risk of TA.
文摘Increasing evidence shows that extremely low frequency electromagnetic fields（ELF-EMFs） stimulation is able to exert a certain action on autoimmunity and immune cells. In the past, the efficacy of pulsed ELFEMFs in alleviating the symptoms and the progression of multiple sclerosis has been supported through their action on neurotransmission and on the autoimmune mechanisms responsible for demyelination. Regarding the immune system, ELF-EMF exposure contributes to a general activation of macrophages, resulting in changes of autoimmunity and several immunological reactions, such as increased reactive oxygen species-formation, enhanced phagocytic activity and increased production of chemokines. Transcranial electromagnetic brain stimulation is a non-invasive novel technique used recently to treat different neurodegenerative disorders, in particular Alzheimer＇s disease. Despite its proven value, the mechanisms through which EMF brain-stimulation exerts its beneficial action on neuronal function remains unclear. Recent studies have shown that its beneficial effects may be due to a neuroprotective effect on oxidative cell damage. On the basis of in vitro and clinical studies on brain activity, modulation by ELF-EMFs could possibly counteract the aberrant pro-inflammatory responses present in neurodegenerative disorders reducing their severity and their onset. The objective of this review is to provide a systematic overview of the published literature on EMFs and outline the most promising effects of ELF-EMFs in developing treatments of neurodegenerative disorders. In this regard, we review data supporting the role of ELF-EMF in generating immune-modulatory responses, neuromodulation, and potential neuroprotective benefits. Nonetheless, we reckon that the underlying mechanisms of interaction between EMF and the immune system are still to be completely understood and need further studies at a molecular level.
文摘BACKGROUND Mesenchymal stem cells(MSCs)have been reported to possess immune regulatory effects in innate and adaptive immune reactions.MSCs can mediate intercellular communications by releasing extracellular vesicles(EVs),which deliver functional molecules to targeted cells.MSC derived EVs(MSC-EVs)confer altering effects on many immune cells,including T lymphocytes,B lymphocytes,natural killer cells,dendritic cells,and macrophages.A large number of studies have suggested that MSC-EVs participate in regulating autoimmunity related diseases.This characteristic of MSC-EVs makes them be potential biomarkers for the diagnosis and treatment of autoimmunity related diseases.AIM To verify the potential of MSC-EVs for molecular targeted therapy of autoimmunity related diseases.METHODS Literature search was conducted in PubMed to retrieve the articles published between 2010 and 2020 in the English language.The keywords,such as“MSCs,”“EVs,”“exosome,”“autoimmunity,”“tumor immunity,”and“transplantation immunity,”and Boolean operator“AND”and“NOT”coalesced admirably to be used for searching studies on the specific molecular mechanisms of MSC-EVs in many immune cell types and many autoimmunity related diseases.Studies that did not investigate the molecular mechanisms of MSC-EVs in the occurrence and development of autoimmune diseases were excluded.RESULTS A total of 96 articles were chosen for final reference lists.After analyzing those publications,we found that it had been well documented that MSC-EVs have the ability to induce multiple immune cells,like T lymphocytes,B lymphocytes,natural killer cells,dendritic cells,and macrophages,to regulate immune responses in innate immunity and adaptive immunity.Many validated EVsdelivered molecules have been identified as key biomarkers,such as proteins,lipids,and nucleotides.Some EVs-encapsulated functional molecules can serve as promising therapeutic targets particularly for autoimmune disease.CONCLUSION MSC-EVs play an equally important part in the differentiation,activation,and proliferation of immune cells,and they may become potential biomarkers for diagnosis and treatment of autoimmunity related diseases.
文摘Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection can give rise to different clinical manifestations that are directly related to viral tissue damage or indirectly induced by the antiviral immune response.Hyper-activation of the immune system in an attempt to eradicate the infection may trigger autoimmunity.Several immune-mediated disorders have been described in SARS-CoV-2-infected individuals.These include cutaneous rashes and vasculitis,autoimmune cytopenia,anti-phospholipid syndrome,central or peripheral neuropathy,myositis and myocarditis.On the other hand,rheumatic patients were reported to have similar coronavirus disease 2019(COVID-19)incidence,morbidity and mortality rates compared to general population.This opinion review will summarize the crucial immunologic steps which occur during SARSCoV-2-infection that may link autoimmunity to COVID-19 and provides an opportunity for further discussion regarding this association.
文摘Primary biliary cirrhosis(PBC) is an autoimmune liver disease characterized by the presence of serum autoantibodies and chronic nonsuppurative destructive cholangitis.The pathogenesis of PBC involves environmental factors,genetic predisposition and loss of immune tolerance.In recent years,it has become univocally accepted that an inappropriately activated immune response is one of the most important factors in PBC.In this study,the role of autoimmunity in PBC is summarized and a feasible research orientation is recommended.
文摘Genomic disruption of Fyn has not been associated with an immune-deficient phenotype, notwithstanding the profound impairment in IL-2 production by T cells derived from Fyn-deficient animals observed in vitro. The results presented demonstrate that Fyn deficient animals succumb to influenza infection ahead of the protective expansion of lung infiltrating T cells and viral clearance observed in wild-type hosts. Formal proof that Fyn-dependent IL-2 production mediates T cell expansion in vivo is provided using a model of T cell induced enteropathy. Specifically, Fyn deficient naive T cells do not induce colitis in SCID animals due to their lack of expansion, and Fyn re-expression rescues both IL-2 production and its capacity to support in vivo expansion leading to colitis. These results reconcile the obligatory role of Fyn in T cell activation and autocrine IL-2 supported growth;and underscore the mechanism through which its function is integrated with and regulated by Lck.
