Primary biliary cholangitis(PBC)is an autoimmune disease characterized by the selective destruction of intrahepatic small bile ducts,primarily by infiltrating lymphocytes,and has limited therapeutic options.A growing ...Primary biliary cholangitis(PBC)is an autoimmune disease characterized by the selective destruction of intrahepatic small bile ducts,primarily by infiltrating lymphocytes,and has limited therapeutic options.A growing body of evidence suggests that nanoparticles encapsulating rapamycin(ImmTOR)can suppress autoreactive lymphocytes and reduce inflammatory cytokine levels in various autoimmune diseases.In a recent study,Yang et al investigated the therapeutic effects of ImmTOR in a mouse model of PBC.ImmTOR treatment reduced the expression and number of CD4+T cells,CD8+T cells,and B cells isolated from the liver and spleen,improved liver inflammation and enzyme levels,and was associated with a concomitant decrease in anti-mitochondrial antibody levels.In this editorial,we highlight the significance of these findings,focusing on the potential mechanisms by which ImmTOR suppresses hepatic autoreactive T cells and reduces anti-mitochondrial antibody levels,ultimately improving liver pa-thology,through pathways such as mammalian target of rapamycin inhibition and autophagy restoration.We also offer a perspective on future research di-rections for PBC in both animal models and in vitro studies.展开更多
This editorial discusses Alpsoy et al’s significant study of prognosis of pancreatic ductal adenocarcinoma(PDAC),which lacks histopathological markers.This study evaluated the synergistic prognolymphocytes.Peritumora...This editorial discusses Alpsoy et al’s significant study of prognosis of pancreatic ductal adenocarcinoma(PDAC),which lacks histopathological markers.This study evaluated the synergistic prognolymphocytes.Peritumoral budding is significantly correlated with tumor volume,while intratumoral budding is closely related to lymph node metastasis.Peritumoral budding and intratumoral budding are confirmed as independent adverse prognostic factors,and their high levels of expression are associated with immature stromal phenotypes,suggesting the key role of epithelial-mesenchymal transition.These breakthrough findings provide a new multidimensional biomarker system for the prognostic assessment of PDAC,and promote the clinical transformation process of incorporating tumor budding indicators into the pathological reporting process.However,the complexity and spatiotemporal heterogeneity of the tumor microenvironment require us to go beyond traditional morphological analysis and move towards multiomics integration and dynamic monitoring.Through standardized pathological assessment,innovative treatment strategies and interdisciplinary collaboration,it is expected to transform tumor microenvironment-related markers into clinically applicable indicators,ultimately improving the treatment predicament of PDAC.This editorial intended to summarize relevant studies and share some of our views,in order to offer perspectives for future research.展开更多
The global incidence of critical illness has been steadily increasing,resulting in higher mortality rates thereby presenting substantial challenges for clinical mana-gement.Among these conditions,sepsis stands out as ...The global incidence of critical illness has been steadily increasing,resulting in higher mortality rates thereby presenting substantial challenges for clinical mana-gement.Among these conditions,sepsis stands out as the leading cause of critical illness,underscoring the urgent need for continued research to enhance patient care and deepen our understanding of its complex pathophysiology.Lympho-cytes play a pivotal role in both innate and adaptive immune responses,acting as key regulators of the balance between pro-inflammatory and anti-inflam-matory processes to preserve immune homeostasis.In the context of sepsis,an impaired immunity has been associated with disrupted lymphocytic metabolic activity,persistent pro-inflammatory state,and subsequent immunosuppression.These disruptions not only impair pathogen clearance but also predispose pati-ents to secondary infections and hinder recovery,highlighting the importance of targeting lymphocyte dysfunction in sepsis management.Moreover,studies have identified absolute lymphocyte counts and derived parameters as promising clinical biomarkers for prognostic assessment and therapeutic decision-making.In particular,neutrophil-to-lymphocyte ratio,and lymphopenia have gained reco-gnition in the literature as a critical prognostic markers and therapeutic target in the management of sepsis.This review aims to elucidate the multifaceted role of lymphocytes in pathophysiology,with a focus on recent advancements in their use as biomarkers and key findings in this evolving field.展开更多
Aim To investigate the chemical constituents from the twigs and leaves of Pithecellobium clypearia Benth and their immunomodulatory effects. Methods The constituents were separated and purified by various chromatograp...Aim To investigate the chemical constituents from the twigs and leaves of Pithecellobium clypearia Benth and their immunomodulatory effects. Methods The constituents were separated and purified by various chromatographic methods and their structures were identified on the basis of spectral analysis. The immufiomodulatory effects of all the compounds were examined by a Con A-induced T lymphocytes proliferation assay. Results Eight compounds were isolated and identified as （-）- epigallocatechin （1）, （-）-5, 7, 3′, 4′, 5′-pentahydroxyflavan （2）, （-）-epigallocatechin-7-gallate （3）, （-）-5, 3′, 4′, 5′-tetrahydroxyfiavan- 7-gallate （4）, quercitin-3-O-α-L-rhamnpyranoside （5）, myricitin-3-O-α-L-rhamnpyranoside （6）, gallic acid （7）, and ethyl gallate （8）, respectively. Conclusion Compounds 3 and 8 were isolated from this genus for the first time, and compound 1 was isolated from this species for the first time. Compound 3 exhibited a strong inhibition on the T lymphocytes proliferation induced by Con A with an IC50 of 4.4 μmol·L^-1.展开更多
BACKGROUND Depression is a significant psychiatric disorder with particularly high prevalence among adolescents.This mental health condition can have severe consequences,including academic failure,social withdrawal,an...BACKGROUND Depression is a significant psychiatric disorder with particularly high prevalence among adolescents.This mental health condition can have severe consequences,including academic failure,social withdrawal,and suicidal behavior.Given the increasing rate of depression in this age group,understanding the underlying biological mechanisms is essential for early detection and intervention.Recent studies have suggested that immune markers play a role in the pathophysiology of depression,prompting further investigation of their potential association with depressive symptoms in adolescents.AIM To investigate the relationship between immune markers(monocytes,lymphocytes,and direct bilirubin)and the incidence and severity of depression among adolescents.METHODS This cross-sectional study recruited 145 adolescent patients with depression[male(M)/female(F)=38/107]from Jiangbin Hospital in Guangxi,Zhuang and 163 healthy controls(M/F=77/86)from routine health check-ups.Blood samples were collected after an overnight fast.Depression severity was measured using the Zung Self-Rating Depression Scale.The inclusion criteria were age 12-24 years,diagnosis of depressive disorder(ICD-10),and no recent antidepressant use.The exclusion criteria included psychiatric comorbidities and serious somatic diseases.Key statistical methods included group comparisons and correlation analyses.RESULTS There was a higher prevalence of females in the depression group(P<0.001).Significant age differences were observed between the groups(Z=9.43,P<0.001).The depression group had higher monocyte(Z=3.43,P<0.001)and lymphocyte(t=2.29,P<0.05)counts,and higher serum direct bilirubin levels(Z=4.72,P<0.001).Monocyte count varied significantly according to depression severity,with lower counts in the mild group(Z=-2.90,P<0.05).A negative correlation between age and lymphocyte counts was observed(ρ=-0.22,P<0.01).Logistic regression analysis showed that serum direct bilirubin levels significantly predicted depression.CONCLUSION The potential role of elevated levels of immune markers in the early detection of depression in adolescents has been highlighted.Therefore,it is necessary to explore further the relationships between these immune markers and depression.展开更多
As the average age of the world population increases,more people will face debilitating aging-associated conditions,including dementia and stroke.Not only does the incidence of these conditions increase with age,but t...As the average age of the world population increases,more people will face debilitating aging-associated conditions,including dementia and stroke.Not only does the incidence of these conditions increase with age,but the recovery afterward is often worse in older patients.Researchers and health professionals must unveil and understand the factors behind age-associated diseases to develop a therapy for older patients.Aging causes profound changes in the immune system including the activation of microglia in the brain.Activated microglia promote T lymphocyte transmigration leading to an increase in neuroinflammation,white matter damage,and cognitive impairment in both older humans and rodents.The presence of T and B lymphocytes is observed in the aged brain and correlates with worse stroke outcomes.Preclinical strategies in stroke target either microglia or the lymphocytes or the communications between them to promote functional recovery in aged subjects.In this review,we examine the role of the microglia and T and B lymphocytes in aging and how they contribute to cognitive impairment.Additionally,we provide an important update on the contribution of these cells and their interactions in preclinical aged stroke.展开更多
Background:Transcription factor Krüppel-like factor 3(KLF3)may be involved in regulating inflammation and lymphocyte function.Immune dysfunction in sepsis involves both hyper-inflammation and immunosuppression.Ho...Background:Transcription factor Krüppel-like factor 3(KLF3)may be involved in regulating inflammation and lymphocyte function.Immune dysfunction in sepsis involves both hyper-inflammation and immunosuppression.However,studies on T-lymphocyte KLF3 expression in sepsis are lacking.Methods:We induced sepsis in mice via cecal ligation and puncture(CLP),and their survival rate over 7 days was evaluated.To identify the immune status of these mice,we assessed their cytokine levels,organ damage scores,and splenic T-lymphocyte phenotype.Finally,T-lymphocyte KLF3 expression was detected through flow cytometry.Results:Over the 7 days of observation,septic mice demonstrated 64.7%mortality.In the early stages after CLP,the proinflammatory and anti-inflammatory cytokine levels increased rapidly,multiple organ damage occurred,and splenic T lymphocytes became activated.However,the proportion of KLF3+T lymphocytes decreased.Subsequently,cytokine levels and lymphocyte activation decreased.An increase in cell apoptosis led to a substantial loss of T lymphocytes.Combined with the continual elevations in serum interleukin levels and worsening severe organ damage,septic mice may have entered a state of persistent inflammation and immunosuppression,with a simultaneous increase in KLF3 expression in T lymphocytes.Notably,KLF3 expression was negatively correlated with T-lymphocyte activation and apoptosis.Conclusions:In our septic mice,splenic T-lymphocyte KLF3 expression decreased in the early stage when the mice exhibited a systemic inflammatory response and T-lymphocyte activation.In contrast,it increased in the later stage,when persistent inflammation and immunosuppression occurred.Dynamic monitoring of KLF3 expression levels may provide aid in identifying the immune status of sepsis.展开更多
Objective：With the regular mixed lymphocytes culture （MLC） to detect the allograft rejection, the reactivity of the activated lymphocytes （primed lymphocytes） of a recipient shows sometimes increase and sometimes...Objective：With the regular mixed lymphocytes culture （MLC） to detect the allograft rejection, the reactivity of the activated lymphocytes （primed lymphocytes） of a recipient shows sometimes increase and sometimes decrease against the antigens from the donor, which is inconsistent with the clinical results. In order to establish a convenient method for testing the specificity of the activated lymphocytes in vitro, so as to know the rejection occurred or not by testing the existence of the specific activated lymphocytes against donor＇s HLA antigens in the recipient＇s peripheral blood. Methods： Anti-IL-2 neutralizing monoclonal antibody （anti-IL-2 N-mAb） and immunosuppressors were introduced in this test system in the presence of specific stimulators and activated lymphocytes. Results ： When the activated lymphocytes were chosen from the one-way MLC 4 d to undergo re-stimulation by specific stimulators, the activity of activated lymphocytes in the treatment group was suppressed significantly compared with that in the control group. The result of this test method is consistent with the biopsy in the clinical diagnosis of rejection. Conclusion：h suggests that the activated lymphocytes can be inactivated by specific antigens in certain conditions. This can be a useful tool to define the specificity of the activated lymphocytes.展开更多
Aim In this study, we investigated the changes of lymphocyte subpopulationand apoptosis process of lymphocytes in the elderly, and the modulatory effect of pollen extract(PE) on apoptosis. Methods Lymphocyte phenotype...Aim In this study, we investigated the changes of lymphocyte subpopulationand apoptosis process of lymphocytes in the elderly, and the modulatory effect of pollen extract(PE) on apoptosis. Methods Lymphocyte phenotypes were detected using indirect immunofluorescencetechnique. The proliferation responses were determined by MTT method. Flow cytometry and automaticimage analysis were performed to evaluate the apoptosis of lymphocytes. Results The proliferationresponses of lymphocytes in the elderly were lower than that in young adults. Decreased CD_(45) RA^+cells and increased CD_(45) RO^+ cells were found in lymphocyte population of aged people, comparedwith that of young adults. The CD_(45) RO^+ cells were prone to apoptosis. There is an inhibitoryeffect of PE on apoptosis of lymphocytes in the elderly. Conclusion It is implied that thesusceptibility of lymphocyte in the elderly to apoptosis depends on activation, so called,activation-induced cell death. Present results suggest that apoptosis of lymphocytes in aged peopleplay an important role in the pathogenesis of immunosenescence. Thus, a possibility is open fordevelopment of apoptosis-modulating drugs from pollen.展开更多
[Objective] This study aimed to investigate the effects of traditional Chinese medicine additives on numbers of lymphocytes and goblet cells in villus epithelia of layers under heat stress.[Method] A total of 180 88-d...[Objective] This study aimed to investigate the effects of traditional Chinese medicine additives on numbers of lymphocytes and goblet cells in villus epithelia of layers under heat stress.[Method] A total of 180 88-d-old healthy Esa Brown cocks were selected.They were randomly divided into 9 experimental groups：Room temperature control,High temperature control,VC addition group,High formula I,Moderate formula I,Low formula I,High formula II,Moderate formula II and Low formula II.The formula I and formula II were to add different herbal extracts to the diet of cocks with different doses.The cocks in the VC addition group were administered orally with same-concentration VC solution.After certain time,the cocks were slaughtered.Then the numbers of epithelial lymphocytes and goblet cells in various segments of small intestine were counted by using conventional histological section and HE staining.[Result] The numbers of lymphocytes and goblet cells in villus epithelia of layers under heat stress were decreased gradually with the proceeding of experiment.The herbal extracts of formula I and formula II all could promote the generation of lymphocytes and goblet cells.But the promoting effect of formula II was best.[Conclusion] The Chinese herbal medicine additives have a good relieving effect on heat stress in layers.展开更多
Apoptosis plays an essential role in T cell biology. Thymocytes expressing nonfunctional or autoreactive TCRs are eliminated by apoptosis during development. Apoptosis also leads to the deletion of expanded effector T...Apoptosis plays an essential role in T cell biology. Thymocytes expressing nonfunctional or autoreactive TCRs are eliminated by apoptosis during development. Apoptosis also leads to the deletion of expanded effector T cells during immune responses. The dysregulation of apoptosis in the immune system results in autoimmunity, tumorogenesis and immunodeficiency. Two major pathways lead to apoptosis: the intrinsic cell death pathway controlled by Bcl-2 family members and the extrinsic cell death pathway controlled by death receptor signaling. These two pathways work to- gether to regulate T lymphocyte development and function.展开更多
Tertiary lymphoid structures(TLS)are ectopic lymphoid structures in cancers that are largely associated with favourable prognosis.However,the prognostic value of TLSs in oral squamous cell carcinoma(OSCC)is largely un...Tertiary lymphoid structures(TLS)are ectopic lymphoid structures in cancers that are largely associated with favourable prognosis.However,the prognostic value of TLSs in oral squamous cell carcinoma(OSCC)is largely unknown,and the association between tumour infiltrating lymphocytes(TILs)and TLSs has been rarely explored in OSCC.In this study,associated markers of TLS,including peripheral node address(PNAd)in high endothelial venules,CD20 in B cells and CD3 in T cells,were examined in 168 OSCC patients,and survival analysis was performed between TLS-positive and TLS-negative cohorts.We detected the presence of TILs by staining CD8+cytotoxic T cells and CD57+NK cells as well.TLSs appeared as highly organized structures in 45(26.8%)cases.TLSpositive patients had a better 5-year overall survival(OS)rate(88.9%vs.56.1%,P<0.001)and relapse-free survival(RFS)rate(88.9%vs.63.4%,P=0.002).Moreover,the presence of TLS was an independent prognostic factor for both the 5-year OS rate(hazard ratio[HR]=3.784;95%confidence interval[CI],1.498–9.562)and RFS rate(HR=3.296;95%CI,1.279–8.490)in multivariate analysis.Furthermore,a higher density of CD8+T cells and CD57+NK cells was found in TLS-positive sections than in TLS-negative counterparts(P<0.001),and their combination provided a higher predictive accuracy(AUC=0.730;95%CI,0.654–0.805).In conclusion,our results suggest that TLS is an independent positive prognostic factor for OSCC patients.These findings provide a theoretical basis for the future diagnostic and therapeutic value of TLSs in OSCC treatment.展开更多
AIM To investigate the expression of perforin and fas ligand (fas L) of tumor infiltrating lymphocytes (TILs) in human hepatocellular carcinoma (HCC). METHODS By in situ hybridization and immunohistochemistry...AIM To investigate the expression of perforin and fas ligand (fas L) of tumor infiltrating lymphocytes (TILs) in human hepatocellular carcinoma (HCC). METHODS By in situ hybridization and immunohistochemistry, the perforin and fas L gene expression of TILs was studied in 20 HCC cases. RESULTS Positive expression of perforin and fas L genes was detected in 16 HCC cases. One patient had expression of perforin and fas L genes in the majority of TILs and survived 1 5 years after tumor resection without HCC relapse. This seems that the presence of a large number of activated T cells might be beneficial for the antitumor immunity. In other cases, less than 10% of TILs were able to express perforin and fas L genes. CONCLUSION Although there were a number of T cells in HCC, only few of them were immunoactive and able to kill tumor cells. It seems important to promote further proliferation of these activated T cells in vitro or in vivo .展开更多
AIM:To investigate the role of tumor inf iltrating lym-phocytes(TIL)in primary hepatocellular and cholangio-lar carcinomas of the liver.METHODS:Immunohistochemical analysis was per-formed including antibodies to CD3,C...AIM:To investigate the role of tumor inf iltrating lym-phocytes(TIL)in primary hepatocellular and cholangio-lar carcinomas of the liver.METHODS:Immunohistochemical analysis was per-formed including antibodies to CD3,CD4,CD8,CD20,CD56 and TIA-1 in formalin-f ixed and paraff in-embed-ded tissue of 35 liver resection specimens of hepatocel-lular or cholangiocellular carcinomas.Semiquantitative evaluation was performed with emphasis on the area of the tumor itself and of the tumor/liver interface.RESULTS:All hepatocellular carcinomas showed in-filtration of lymphocytes predominantly around the tumor in the tumor/liver interface consisting mainly of CD3+CD4+T lymphocytes[164.3/10 high power f ields(HPF)]and in the tumor itself of CD8+cells(54.9/10 HPF).Cholangiocarcinomas contained a heterogeneous amount of TIL,composed mainly of CD3+T cells with a predominance of CD8+cells in the tumor tissue(52.6/10 HPF)and of CD4+cells in the interface region(223.1/10 HPF).CD56+cells of the innate immune system were scarce.There was no significant difference between hepatocellular or cholangiolar carcinoma.No correlation with the clinicopathological data was seen.CONCLUSION:Liver TIL consists of intratumoral CD8+T cells and peritumoral CD4+T cells indepen-dent of histogenetic origin.Different functions of lym-phocytes in these regions seem possible.展开更多
Objective To explore the effects of Sterigmatocystin (ST), Deoxynivalenol (DON) and Aflatoxin G1 (AFG1) on apoptosis of human peripheral blood lymphocytes (HPBLs) in vitro and thus to further elucidate the putative r...Objective To explore the effects of Sterigmatocystin (ST), Deoxynivalenol (DON) and Aflatoxin G1 (AFG1) on apoptosis of human peripheral blood lymphocytes (HPBLs) in vitro and thus to further elucidate the putative roles of these three mycotoxins on human immunosystem. Methods The effects of ST, DON and AFG1 on apoptosis of HPBLs were studied with cell culture, flow cytometric (FCM) DNA analysis and DNA agarose gel electrophoresis. Results DNA agarose gel electrophoresis results showed the characteristic 'ladder' pattern of apoptosis in HPBLs treated with ST, DON and AFG1. Flow cytometric DNA analysis revealed that typical subdiploid peaks of apoptosis in DNA histogram could be seen in all groups treated with the three mycotoxins. Significant time-effect and dose-effect relationships were found between the apoptosis rates and treatment time as well as concentrations of the three mycotoxins. Conclusion ST, DON and AFG1 can induce apoptosis of HPBLs in vitro and may have some negative effects on human immunosystem.展开更多
In this study, the IL-2 mRNA levels of T lymphocytes in normal mice stimulated by nine Chinese herbal medicinal ingredients （CHMIs） were measured using semiquantification reverse transcription polymerase chain react...In this study, the IL-2 mRNA levels of T lymphocytes in normal mice stimulated by nine Chinese herbal medicinal ingredients （CHMIs） were measured using semiquantification reverse transcription polymerase chain reaction. The results showed that astragalus polysaccharide （APS）, epimedium polysaccharide （EPS）, Chinese angelica polysaccharide （CAPS）, propolis flavone （PF）, and astrogalosides （AS） promoted IL-2 mRNA levels in T lymphocytes in vitro and in vivo to differing degrees, and the level of IL-2 mRNA induced by propolis polysaccharide （PPS） in vitro was higher than that induced by the control, which differed from that of PPS in vivo.展开更多
Celiac disease(CD)is a chronic immune-mediated disorder triggered by the ingestion of gluten in genetically predisposed individuals.Before activating the immune system,gluten peptides are transferred by the epithelial...Celiac disease(CD)is a chronic immune-mediated disorder triggered by the ingestion of gluten in genetically predisposed individuals.Before activating the immune system,gluten peptides are transferred by the epithelial barrier to the mucosal lamina propria,where they are deamidated by intestinal tissue transglutaminase 2.As a result,they strongly bind to human leucocyte antigens(HLAs),especially HLA-DQ2 and HLA-DQ8,expressed on antigen-presenting cells.This induces an inflammatory response,which results in small bowel enteropathy.Although gluten is the main external trigger activating both innate and adaptive(specific)immunity,its presence in the intestinal lumen does not fully explain CD pathogenesis.It has been hypothesized that an early disruption of the gut barrier in genetically susceptible individuals,which would result in an increased intestinal permeability,could precede the onset of gluten-induced immune events.The intestinal barrier is a complex functional structure,whose functioning is dependent on intestinal microbiotahomeostasis,epithelial layer integrity,and the gutassociated lymphoid tissue with its intraepithelial lymphocytes(IELs).The aim of this paper was to review the current literature and summarize the role of the gut microbiota,epithelial cells and their intercellular junctions,and IELs in CD development.展开更多
Objective To study the effect of spleen lymphocytes on the splenomegaly by hepatocellular carcinoma-bearing mouse model. Methods Cell counts, cell cycle distribution, the percentage of lymphocytes subsets and the leve...Objective To study the effect of spleen lymphocytes on the splenomegaly by hepatocellular carcinoma-bearing mouse model. Methods Cell counts, cell cycle distribution, the percentage of lymphocytes subsets and the levels of iL-2 were measured, and two-dimensional gel electrophoresis （2-DE） was used to investigate the relationship between spleen lymphocytes and splenomegaly in hepatocellular carcinoma-bearing mice. Results Compared with the normal group, the thymus was obviously atrophied and the spleen was significantly enlarged in the tumor-bearing group. Correlation study showed that the number of whoJe spleen cells was positively correlated with the splenic index. The cell diameter and cell-cycle phase distribution of splenocytes in the tumor-bearing group showed no significant difference compared to the normal group. The percentage of CD3＋ T lymphocytes and CD8＋ T lymphocytes in spleen and peripheral blood of tumor-bearing mice were substantially higher than that in the normal mice. Meanwhile, the IL-2 level was also higher in the tumor-bearing group than in the normal group. Furthermore, two dysregulated protein, β-actin and .S100-A9 were identified in spleen lymphocytes from H22-bearing mice, which were closely related to cellular motility. Conclusion It is suggested that dysregulated β-actin and S100-A9 can result in recirculating T lymphocytes trapped in the spleen, which may explain the underlying cause of splenomegaly in H22-bearing mice.展开更多
In the bone marrow, B cells and bone-resorbing osteoclasts colocalize and form a specific microenvironment. How B cells functionally influence osteoclasts and bone architecture is poorly understood. Using genetically ...In the bone marrow, B cells and bone-resorbing osteoclasts colocalize and form a specific microenvironment. How B cells functionally influence osteoclasts and bone architecture is poorly understood. Using genetically modified mice and highthroughput analyses, we demonstrate that prolonged HIF-1α signaling in B cells leads to enhanced RANKL production and osteoclast formation. In addition, deletion of HIF-1α in B cells prevents estrogen deficiency-induced bone loss in mice.Mechanistically, estrogen controls HIF-1α protein stabilization through HSP70-mediated degradation in bone marrow B cells.The stabilization of HIF-1α protein in HSP70-deficient bone marrow B cells promotes RANKL production and osteoclastogenesis.Induction of HSP70 expression by geranylgeranylacetone(GGA) administration alleviates ovariectomy-induced osteoporosis.Moreover, RANKL gene expression has a positive correlation with HIF1 A expression in human B cells. In conclusion, HIF-1αsignaling in B cells is crucial for the control of osteoclastogenesis, and the HSP70/HIF-1α axis may serve as a new therapeutic target for osteoporosis.展开更多
文摘Primary biliary cholangitis(PBC)is an autoimmune disease characterized by the selective destruction of intrahepatic small bile ducts,primarily by infiltrating lymphocytes,and has limited therapeutic options.A growing body of evidence suggests that nanoparticles encapsulating rapamycin(ImmTOR)can suppress autoreactive lymphocytes and reduce inflammatory cytokine levels in various autoimmune diseases.In a recent study,Yang et al investigated the therapeutic effects of ImmTOR in a mouse model of PBC.ImmTOR treatment reduced the expression and number of CD4+T cells,CD8+T cells,and B cells isolated from the liver and spleen,improved liver inflammation and enzyme levels,and was associated with a concomitant decrease in anti-mitochondrial antibody levels.In this editorial,we highlight the significance of these findings,focusing on the potential mechanisms by which ImmTOR suppresses hepatic autoreactive T cells and reduces anti-mitochondrial antibody levels,ultimately improving liver pa-thology,through pathways such as mammalian target of rapamycin inhibition and autophagy restoration.We also offer a perspective on future research di-rections for PBC in both animal models and in vitro studies.
基金Supported by National Natural Science Foundation of China,No.82404058Shanghai Municipal Commission of Health and Family Planning,No.2024ZZ2049Beijing Xisike Clinical Oncology Research Foundation,No.Y-HS202401-0011.
文摘This editorial discusses Alpsoy et al’s significant study of prognosis of pancreatic ductal adenocarcinoma(PDAC),which lacks histopathological markers.This study evaluated the synergistic prognolymphocytes.Peritumoral budding is significantly correlated with tumor volume,while intratumoral budding is closely related to lymph node metastasis.Peritumoral budding and intratumoral budding are confirmed as independent adverse prognostic factors,and their high levels of expression are associated with immature stromal phenotypes,suggesting the key role of epithelial-mesenchymal transition.These breakthrough findings provide a new multidimensional biomarker system for the prognostic assessment of PDAC,and promote the clinical transformation process of incorporating tumor budding indicators into the pathological reporting process.However,the complexity and spatiotemporal heterogeneity of the tumor microenvironment require us to go beyond traditional morphological analysis and move towards multiomics integration and dynamic monitoring.Through standardized pathological assessment,innovative treatment strategies and interdisciplinary collaboration,it is expected to transform tumor microenvironment-related markers into clinically applicable indicators,ultimately improving the treatment predicament of PDAC.This editorial intended to summarize relevant studies and share some of our views,in order to offer perspectives for future research.
文摘The global incidence of critical illness has been steadily increasing,resulting in higher mortality rates thereby presenting substantial challenges for clinical mana-gement.Among these conditions,sepsis stands out as the leading cause of critical illness,underscoring the urgent need for continued research to enhance patient care and deepen our understanding of its complex pathophysiology.Lympho-cytes play a pivotal role in both innate and adaptive immune responses,acting as key regulators of the balance between pro-inflammatory and anti-inflam-matory processes to preserve immune homeostasis.In the context of sepsis,an impaired immunity has been associated with disrupted lymphocytic metabolic activity,persistent pro-inflammatory state,and subsequent immunosuppression.These disruptions not only impair pathogen clearance but also predispose pati-ents to secondary infections and hinder recovery,highlighting the importance of targeting lymphocyte dysfunction in sepsis management.Moreover,studies have identified absolute lymphocyte counts and derived parameters as promising clinical biomarkers for prognostic assessment and therapeutic decision-making.In particular,neutrophil-to-lymphocyte ratio,and lymphopenia have gained reco-gnition in the literature as a critical prognostic markers and therapeutic target in the management of sepsis.This review aims to elucidate the multifaceted role of lymphocytes in pathophysiology,with a focus on recent advancements in their use as biomarkers and key findings in this evolving field.
文摘Aim To investigate the chemical constituents from the twigs and leaves of Pithecellobium clypearia Benth and their immunomodulatory effects. Methods The constituents were separated and purified by various chromatographic methods and their structures were identified on the basis of spectral analysis. The immufiomodulatory effects of all the compounds were examined by a Con A-induced T lymphocytes proliferation assay. Results Eight compounds were isolated and identified as （-）- epigallocatechin （1）, （-）-5, 7, 3′, 4′, 5′-pentahydroxyflavan （2）, （-）-epigallocatechin-7-gallate （3）, （-）-5, 3′, 4′, 5′-tetrahydroxyfiavan- 7-gallate （4）, quercitin-3-O-α-L-rhamnpyranoside （5）, myricitin-3-O-α-L-rhamnpyranoside （6）, gallic acid （7）, and ethyl gallate （8）, respectively. Conclusion Compounds 3 and 8 were isolated from this genus for the first time, and compound 1 was isolated from this species for the first time. Compound 3 exhibited a strong inhibition on the T lymphocytes proliferation induced by Con A with an IC50 of 4.4 μmol·L^-1.
基金Supported by the Medical Discipline Construction Project of Pudong Health Committee of Shanghai,No.PWZzb2022-09Nanning City Science Research and Technology Development Program,No.ZC20233017and Guangxi Medical and Health Appropriate Technology Development and Promotion Project,No.S2021061.
文摘BACKGROUND Depression is a significant psychiatric disorder with particularly high prevalence among adolescents.This mental health condition can have severe consequences,including academic failure,social withdrawal,and suicidal behavior.Given the increasing rate of depression in this age group,understanding the underlying biological mechanisms is essential for early detection and intervention.Recent studies have suggested that immune markers play a role in the pathophysiology of depression,prompting further investigation of their potential association with depressive symptoms in adolescents.AIM To investigate the relationship between immune markers(monocytes,lymphocytes,and direct bilirubin)and the incidence and severity of depression among adolescents.METHODS This cross-sectional study recruited 145 adolescent patients with depression[male(M)/female(F)=38/107]from Jiangbin Hospital in Guangxi,Zhuang and 163 healthy controls(M/F=77/86)from routine health check-ups.Blood samples were collected after an overnight fast.Depression severity was measured using the Zung Self-Rating Depression Scale.The inclusion criteria were age 12-24 years,diagnosis of depressive disorder(ICD-10),and no recent antidepressant use.The exclusion criteria included psychiatric comorbidities and serious somatic diseases.Key statistical methods included group comparisons and correlation analyses.RESULTS There was a higher prevalence of females in the depression group(P<0.001).Significant age differences were observed between the groups(Z=9.43,P<0.001).The depression group had higher monocyte(Z=3.43,P<0.001)and lymphocyte(t=2.29,P<0.05)counts,and higher serum direct bilirubin levels(Z=4.72,P<0.001).Monocyte count varied significantly according to depression severity,with lower counts in the mild group(Z=-2.90,P<0.05).A negative correlation between age and lymphocyte counts was observed(ρ=-0.22,P<0.01).Logistic regression analysis showed that serum direct bilirubin levels significantly predicted depression.CONCLUSION The potential role of elevated levels of immune markers in the early detection of depression in adolescents has been highlighted.Therefore,it is necessary to explore further the relationships between these immune markers and depression.
基金supported by 16POST27490032 American Heart Association post-doctoral fellowshipNational Institute of Neurological Disorders and Stroke Exploratory Neuroscience Research Grant R21 NS114836-01A1 (to AC)
文摘As the average age of the world population increases,more people will face debilitating aging-associated conditions,including dementia and stroke.Not only does the incidence of these conditions increase with age,but the recovery afterward is often worse in older patients.Researchers and health professionals must unveil and understand the factors behind age-associated diseases to develop a therapy for older patients.Aging causes profound changes in the immune system including the activation of microglia in the brain.Activated microglia promote T lymphocyte transmigration leading to an increase in neuroinflammation,white matter damage,and cognitive impairment in both older humans and rodents.The presence of T and B lymphocytes is observed in the aged brain and correlates with worse stroke outcomes.Preclinical strategies in stroke target either microglia or the lymphocytes or the communications between them to promote functional recovery in aged subjects.In this review,we examine the role of the microglia and T and B lymphocytes in aging and how they contribute to cognitive impairment.Additionally,we provide an important update on the contribution of these cells and their interactions in preclinical aged stroke.
基金supported by grants from theNational Key Specialty Construction Project of China[grant number 2023-141]the National High Level Hospital Clinical Research Funding(Scientific Research Feed Fund of Peking University First Hospital)[grant number 2022SF23].
文摘Background:Transcription factor Krüppel-like factor 3(KLF3)may be involved in regulating inflammation and lymphocyte function.Immune dysfunction in sepsis involves both hyper-inflammation and immunosuppression.However,studies on T-lymphocyte KLF3 expression in sepsis are lacking.Methods:We induced sepsis in mice via cecal ligation and puncture(CLP),and their survival rate over 7 days was evaluated.To identify the immune status of these mice,we assessed their cytokine levels,organ damage scores,and splenic T-lymphocyte phenotype.Finally,T-lymphocyte KLF3 expression was detected through flow cytometry.Results:Over the 7 days of observation,septic mice demonstrated 64.7%mortality.In the early stages after CLP,the proinflammatory and anti-inflammatory cytokine levels increased rapidly,multiple organ damage occurred,and splenic T lymphocytes became activated.However,the proportion of KLF3+T lymphocytes decreased.Subsequently,cytokine levels and lymphocyte activation decreased.An increase in cell apoptosis led to a substantial loss of T lymphocytes.Combined with the continual elevations in serum interleukin levels and worsening severe organ damage,septic mice may have entered a state of persistent inflammation and immunosuppression,with a simultaneous increase in KLF3 expression in T lymphocytes.Notably,KLF3 expression was negatively correlated with T-lymphocyte activation and apoptosis.Conclusions:In our septic mice,splenic T-lymphocyte KLF3 expression decreased in the early stage when the mice exhibited a systemic inflammatory response and T-lymphocyte activation.In contrast,it increased in the later stage,when persistent inflammation and immunosuppression occurred.Dynamic monitoring of KLF3 expression levels may provide aid in identifying the immune status of sepsis.
文摘Objective：With the regular mixed lymphocytes culture （MLC） to detect the allograft rejection, the reactivity of the activated lymphocytes （primed lymphocytes） of a recipient shows sometimes increase and sometimes decrease against the antigens from the donor, which is inconsistent with the clinical results. In order to establish a convenient method for testing the specificity of the activated lymphocytes in vitro, so as to know the rejection occurred or not by testing the existence of the specific activated lymphocytes against donor＇s HLA antigens in the recipient＇s peripheral blood. Methods： Anti-IL-2 neutralizing monoclonal antibody （anti-IL-2 N-mAb） and immunosuppressors were introduced in this test system in the presence of specific stimulators and activated lymphocytes. Results ： When the activated lymphocytes were chosen from the one-way MLC 4 d to undergo re-stimulation by specific stimulators, the activity of activated lymphocytes in the treatment group was suppressed significantly compared with that in the control group. The result of this test method is consistent with the biopsy in the clinical diagnosis of rejection. Conclusion：h suggests that the activated lymphocytes can be inactivated by specific antigens in certain conditions. This can be a useful tool to define the specificity of the activated lymphocytes.
文摘Aim In this study, we investigated the changes of lymphocyte subpopulationand apoptosis process of lymphocytes in the elderly, and the modulatory effect of pollen extract(PE) on apoptosis. Methods Lymphocyte phenotypes were detected using indirect immunofluorescencetechnique. The proliferation responses were determined by MTT method. Flow cytometry and automaticimage analysis were performed to evaluate the apoptosis of lymphocytes. Results The proliferationresponses of lymphocytes in the elderly were lower than that in young adults. Decreased CD_(45) RA^+cells and increased CD_(45) RO^+ cells were found in lymphocyte population of aged people, comparedwith that of young adults. The CD_(45) RO^+ cells were prone to apoptosis. There is an inhibitoryeffect of PE on apoptosis of lymphocytes in the elderly. Conclusion It is implied that thesusceptibility of lymphocyte in the elderly to apoptosis depends on activation, so called,activation-induced cell death. Present results suggest that apoptosis of lymphocytes in aged peopleplay an important role in the pathogenesis of immunosenescence. Thus, a possibility is open fordevelopment of apoptosis-modulating drugs from pollen.
基金Supported by National Natural Science Foundation of China(31472230)Hebei Provinceial Natrual Science Foundation of China(2014407068)Project of HebeiScience and Technology Department(14966610D,13826615D,12220408D)~~
文摘[Objective] This study aimed to investigate the effects of traditional Chinese medicine additives on numbers of lymphocytes and goblet cells in villus epithelia of layers under heat stress.[Method] A total of 180 88-d-old healthy Esa Brown cocks were selected.They were randomly divided into 9 experimental groups：Room temperature control,High temperature control,VC addition group,High formula I,Moderate formula I,Low formula I,High formula II,Moderate formula II and Low formula II.The formula I and formula II were to add different herbal extracts to the diet of cocks with different doses.The cocks in the VC addition group were administered orally with same-concentration VC solution.After certain time,the cocks were slaughtered.Then the numbers of epithelial lymphocytes and goblet cells in various segments of small intestine were counted by using conventional histological section and HE staining.[Result] The numbers of lymphocytes and goblet cells in villus epithelia of layers under heat stress were decreased gradually with the proceeding of experiment.The herbal extracts of formula I and formula II all could promote the generation of lymphocytes and goblet cells.But the promoting effect of formula II was best.[Conclusion] The Chinese herbal medicine additives have a good relieving effect on heat stress in layers.
基金National Institutes of Health grant CA92123 and American Cancer Society grant RSG-0125201(to YW HE).
文摘Apoptosis plays an essential role in T cell biology. Thymocytes expressing nonfunctional or autoreactive TCRs are eliminated by apoptosis during development. Apoptosis also leads to the deletion of expanded effector T cells during immune responses. The dysregulation of apoptosis in the immune system results in autoimmunity, tumorogenesis and immunodeficiency. Two major pathways lead to apoptosis: the intrinsic cell death pathway controlled by Bcl-2 family members and the extrinsic cell death pathway controlled by death receptor signaling. These two pathways work to- gether to regulate T lymphocyte development and function.
基金This work was supported by the National Natural Science Foundations of China(Nos.81972532,81772896,81602383 and 81472524)the Science and Technology Planning Project of Guangzhou City of China(No.2017004020102).
文摘Tertiary lymphoid structures(TLS)are ectopic lymphoid structures in cancers that are largely associated with favourable prognosis.However,the prognostic value of TLSs in oral squamous cell carcinoma(OSCC)is largely unknown,and the association between tumour infiltrating lymphocytes(TILs)and TLSs has been rarely explored in OSCC.In this study,associated markers of TLS,including peripheral node address(PNAd)in high endothelial venules,CD20 in B cells and CD3 in T cells,were examined in 168 OSCC patients,and survival analysis was performed between TLS-positive and TLS-negative cohorts.We detected the presence of TILs by staining CD8+cytotoxic T cells and CD57+NK cells as well.TLSs appeared as highly organized structures in 45(26.8%)cases.TLSpositive patients had a better 5-year overall survival(OS)rate(88.9%vs.56.1%,P<0.001)and relapse-free survival(RFS)rate(88.9%vs.63.4%,P=0.002).Moreover,the presence of TLS was an independent prognostic factor for both the 5-year OS rate(hazard ratio[HR]=3.784;95%confidence interval[CI],1.498–9.562)and RFS rate(HR=3.296;95%CI,1.279–8.490)in multivariate analysis.Furthermore,a higher density of CD8+T cells and CD57+NK cells was found in TLS-positive sections than in TLS-negative counterparts(P<0.001),and their combination provided a higher predictive accuracy(AUC=0.730;95%CI,0.654–0.805).In conclusion,our results suggest that TLS is an independent positive prognostic factor for OSCC patients.These findings provide a theoretical basis for the future diagnostic and therapeutic value of TLSs in OSCC treatment.
文摘AIM To investigate the expression of perforin and fas ligand (fas L) of tumor infiltrating lymphocytes (TILs) in human hepatocellular carcinoma (HCC). METHODS By in situ hybridization and immunohistochemistry, the perforin and fas L gene expression of TILs was studied in 20 HCC cases. RESULTS Positive expression of perforin and fas L genes was detected in 16 HCC cases. One patient had expression of perforin and fas L genes in the majority of TILs and survived 1 5 years after tumor resection without HCC relapse. This seems that the presence of a large number of activated T cells might be beneficial for the antitumor immunity. In other cases, less than 10% of TILs were able to express perforin and fas L genes. CONCLUSION Although there were a number of T cells in HCC, only few of them were immunoactive and able to kill tumor cells. It seems important to promote further proliferation of these activated T cells in vitro or in vivo .
基金Supported by Centre of Molecular Medicine Cologne(CMMC),Köln,Germany
文摘AIM:To investigate the role of tumor inf iltrating lym-phocytes(TIL)in primary hepatocellular and cholangio-lar carcinomas of the liver.METHODS:Immunohistochemical analysis was per-formed including antibodies to CD3,CD4,CD8,CD20,CD56 and TIA-1 in formalin-f ixed and paraff in-embed-ded tissue of 35 liver resection specimens of hepatocel-lular or cholangiocellular carcinomas.Semiquantitative evaluation was performed with emphasis on the area of the tumor itself and of the tumor/liver interface.RESULTS:All hepatocellular carcinomas showed in-filtration of lymphocytes predominantly around the tumor in the tumor/liver interface consisting mainly of CD3+CD4+T lymphocytes[164.3/10 high power f ields(HPF)]and in the tumor itself of CD8+cells(54.9/10 HPF).Cholangiocarcinomas contained a heterogeneous amount of TIL,composed mainly of CD3+T cells with a predominance of CD8+cells in the tumor tissue(52.6/10 HPF)and of CD4+cells in the interface region(223.1/10 HPF).CD56+cells of the innate immune system were scarce.There was no significant difference between hepatocellular or cholangiolar carcinoma.No correlation with the clinicopathological data was seen.CONCLUSION:Liver TIL consists of intratumoral CD8+T cells and peritumoral CD4+T cells indepen-dent of histogenetic origin.Different functions of lym-phocytes in these regions seem possible.
基金This work is supported by Natural Science Foundation of Hebei Province (No.3972537) A Grant from Ministry of Education of China for Young Teachers (HB-016).
文摘Objective To explore the effects of Sterigmatocystin (ST), Deoxynivalenol (DON) and Aflatoxin G1 (AFG1) on apoptosis of human peripheral blood lymphocytes (HPBLs) in vitro and thus to further elucidate the putative roles of these three mycotoxins on human immunosystem. Methods The effects of ST, DON and AFG1 on apoptosis of HPBLs were studied with cell culture, flow cytometric (FCM) DNA analysis and DNA agarose gel electrophoresis. Results DNA agarose gel electrophoresis results showed the characteristic 'ladder' pattern of apoptosis in HPBLs treated with ST, DON and AFG1. Flow cytometric DNA analysis revealed that typical subdiploid peaks of apoptosis in DNA histogram could be seen in all groups treated with the three mycotoxins. Significant time-effect and dose-effect relationships were found between the apoptosis rates and treatment time as well as concentrations of the three mycotoxins. Conclusion ST, DON and AFG1 can induce apoptosis of HPBLs in vitro and may have some negative effects on human immunosystem.
基金This work was supported by the National Natural Science Foundation of China(30070566).
文摘In this study, the IL-2 mRNA levels of T lymphocytes in normal mice stimulated by nine Chinese herbal medicinal ingredients （CHMIs） were measured using semiquantification reverse transcription polymerase chain reaction. The results showed that astragalus polysaccharide （APS）, epimedium polysaccharide （EPS）, Chinese angelica polysaccharide （CAPS）, propolis flavone （PF）, and astrogalosides （AS） promoted IL-2 mRNA levels in T lymphocytes in vitro and in vivo to differing degrees, and the level of IL-2 mRNA induced by propolis polysaccharide （PPS） in vitro was higher than that induced by the control, which differed from that of PPS in vivo.
基金Supported by the Children’s Memorial Health Institute Grants,No.236/15,No.243/16 and No.S147/2016
文摘Celiac disease(CD)is a chronic immune-mediated disorder triggered by the ingestion of gluten in genetically predisposed individuals.Before activating the immune system,gluten peptides are transferred by the epithelial barrier to the mucosal lamina propria,where they are deamidated by intestinal tissue transglutaminase 2.As a result,they strongly bind to human leucocyte antigens(HLAs),especially HLA-DQ2 and HLA-DQ8,expressed on antigen-presenting cells.This induces an inflammatory response,which results in small bowel enteropathy.Although gluten is the main external trigger activating both innate and adaptive(specific)immunity,its presence in the intestinal lumen does not fully explain CD pathogenesis.It has been hypothesized that an early disruption of the gut barrier in genetically susceptible individuals,which would result in an increased intestinal permeability,could precede the onset of gluten-induced immune events.The intestinal barrier is a complex functional structure,whose functioning is dependent on intestinal microbiotahomeostasis,epithelial layer integrity,and the gutassociated lymphoid tissue with its intraepithelial lymphocytes(IELs).The aim of this paper was to review the current literature and summarize the role of the gut microbiota,epithelial cells and their intercellular junctions,and IELs in CD development.
基金supported by program for Changjiang Scholars and Innovative Research Team in University(IRT1166)National Natural Science Foundation of China(No.31271975)
文摘Objective To study the effect of spleen lymphocytes on the splenomegaly by hepatocellular carcinoma-bearing mouse model. Methods Cell counts, cell cycle distribution, the percentage of lymphocytes subsets and the levels of iL-2 were measured, and two-dimensional gel electrophoresis （2-DE） was used to investigate the relationship between spleen lymphocytes and splenomegaly in hepatocellular carcinoma-bearing mice. Results Compared with the normal group, the thymus was obviously atrophied and the spleen was significantly enlarged in the tumor-bearing group. Correlation study showed that the number of whoJe spleen cells was positively correlated with the splenic index. The cell diameter and cell-cycle phase distribution of splenocytes in the tumor-bearing group showed no significant difference compared to the normal group. The percentage of CD3＋ T lymphocytes and CD8＋ T lymphocytes in spleen and peripheral blood of tumor-bearing mice were substantially higher than that in the normal mice. Meanwhile, the IL-2 level was also higher in the tumor-bearing group than in the normal group. Furthermore, two dysregulated protein, β-actin and .S100-A9 were identified in spleen lymphocytes from H22-bearing mice, which were closely related to cellular motility. Conclusion It is suggested that dysregulated β-actin and S100-A9 can result in recirculating T lymphocytes trapped in the spleen, which may explain the underlying cause of splenomegaly in H22-bearing mice.
文摘In the bone marrow, B cells and bone-resorbing osteoclasts colocalize and form a specific microenvironment. How B cells functionally influence osteoclasts and bone architecture is poorly understood. Using genetically modified mice and highthroughput analyses, we demonstrate that prolonged HIF-1α signaling in B cells leads to enhanced RANKL production and osteoclast formation. In addition, deletion of HIF-1α in B cells prevents estrogen deficiency-induced bone loss in mice.Mechanistically, estrogen controls HIF-1α protein stabilization through HSP70-mediated degradation in bone marrow B cells.The stabilization of HIF-1α protein in HSP70-deficient bone marrow B cells promotes RANKL production and osteoclastogenesis.Induction of HSP70 expression by geranylgeranylacetone(GGA) administration alleviates ovariectomy-induced osteoporosis.Moreover, RANKL gene expression has a positive correlation with HIF1 A expression in human B cells. In conclusion, HIF-1αsignaling in B cells is crucial for the control of osteoclastogenesis, and the HSP70/HIF-1α axis may serve as a new therapeutic target for osteoporosis.
