In the gut of patients with Crohn's disease and patients with ulcerative colitis,the major forms of inflammatory bowel diseases(IBD) in humans,the tissue-damaging immune response is mediated by an active cross-tal...In the gut of patients with Crohn's disease and patients with ulcerative colitis,the major forms of inflammatory bowel diseases(IBD) in humans,the tissue-damaging immune response is mediated by an active cross-talk between immune and non-immune cells.Accumulating evidence indicates also that cytokines produced by these cells play a major role in initiating and shaping this pathologic process.One such cytokine seems to be interleukin(IL)-21,a member of the common γ-chainreceptor family.IL-21 is produced in excess in the in-flamed intestine of patients with IBD mostly by activated CD4+ T helper cells co-expressing interferon-γ and follicular T helper cells.Moreover,both in vitro and in vivo studies indicate that excessive IL-21 production leads to the activation of multiple signaling pathways that expand and sustain the ongoing mucosal inflammation.In this article,we review the available data supporting the pathogenic role of IL-21 in IBD.展开更多
BACKGROUND The single nucleotide polymorphisms of interleukin-21(IL-21)gene were confirmed to be related to various diseases,but no studies have examined the possible role of IL-21 single nucleotide polymorphisms(SNPs...BACKGROUND The single nucleotide polymorphisms of interleukin-21(IL-21)gene were confirmed to be related to various diseases,but no studies have examined the possible role of IL-21 single nucleotide polymorphisms(SNPs)(rs907715,rs2221903,and rs12508721)in gastric precancerous lesions.AIM To explore the associations between SNPs of IL-21 gene(rs907715,rs2221903,and rs12508721)and gastric precancerous lesions in a Chinese population.METHODS Three SNPs of IL-21 were genotyped using polymerase chain reaction–ligase detection reaction in 588 cases and 290 healthy controls from May 2013 to December 2016 in northwestern China.Gastric precancerous lesions were confirmed by endoscopic examination and categorized as non-atrophic gastritis,atrophic gastritis,and intestinal metaplasia.Descriptive statistic and logistic regression were used for data analyses.RESULTS IL-21 rs907715 genotype CC and C frequencies were higher in in patients with gastric precancerous lesions than in the controls(OR=1.59,95%CI:1.06-2.38,P=0.013;OR=1.28,95%CI:1.01-2.22,P=0.044,respectively)after adjusting for confounding factors.For SNP rs907715 in intestinal metaplasia patients,significant differences between cases and controls were observed in the frequencies of genotype CC and C(OR=1.92,95%CI:1.24-2.98,P=0.004;OR=1.53,95%CI:1.04-2.24,P=0.028,respectively);for non-atrophic gastritis and atrophic gastritis patients,the CC and C genotypes showed no significant association with risk in all models.No association between either rs2221903 or rs12508721 and gastric precancerous lesions was found in the present study.In the haplotype analysis,the TC haplotype(rs907715 and rs12508721)and TT haplotype(rs2221903 and rs907715)were more frequent in the case group than control group(P<0.05).CONCLUSION Our findings indicate that SNP rs907715 of IL-21 gene is associated with gastric precancerous lesions.The TC haplotype(rs907715 and rs12508721)and TT haplotype(rs2221903 and rs907715)increased the risk of gastric precancerous lesions.If confirmed,these findings will shed light on the etiology of precancerous lesions.展开更多
BACKGROUND Although expression of interleukin(IL)-34 is upregulated in active ulcerative colitis(UC),the molecular function and underlying mechanism are largely unclear.AIM To investigate the function of IL-34 in acut...BACKGROUND Although expression of interleukin(IL)-34 is upregulated in active ulcerative colitis(UC),the molecular function and underlying mechanism are largely unclear.AIM To investigate the function of IL-34 in acute colitis,in a wound healing model and in colitis-associated cancer in IL-34-deficient mice.METHODS Colitis was induced by administration of dextran sodium sulfate(DSS),and carcinogenesis was induced by azoxymethane(AOM).Whether the impact of IL-34 on colitis was dependent on macrophages was validated by depletion of macrophages in a murine model.The association between IL-34 expression and epithelial proliferation was studied in patients with active UC.RESULTS IL-34 deficiency aggravated murine colitis in acute colitis and in wound healing phase.The effect of IL-34 on experimental colitis was not dependent on macrophage differentiation and polarization.IL-34-deficient mice developed more tumors than wild-type mice following administration of AOM and DSS.No significant difference was shown in degree of cellular differentiation in tumors between wild-type and IL-34-deficient mice.IL-34 was dramatically increased in the active UC patients as previously reported.More importantly,expression of IL-34 was positively correlated with epithelial cell proliferation in patients with UC.CONCLUSION IL-34 deficiency exacerbates colonic inflammation and accelerates colitis-associated carcinogenesis in mice.It might be served as a potential therapeutic target in UC.展开更多
I nterleukin （I L）-21, a cytokine produced by activated CD4＋ T cells, has broad pleiotropic actions that affect the functions of a variety of lymphoid cells. The roles of IL-21 in modulating immunity to infections ...I nterleukin （I L）-21, a cytokine produced by activated CD4＋ T cells, has broad pleiotropic actions that affect the functions of a variety of lymphoid cells. The roles of IL-21 in modulating immunity to infections are currently being defined. Notably, IL-21-mediated cellular and humoral immune responses play an important role in determining the outcome of viral infection. This article reviews the current knowledge on the critical role of IL-21 in hepatitis B virus （HBV） infection. As a competent intermediary, IL-21 derived from virus-specific CD4＋ T cells plays key roles in sustaining CD8＋ T cells and promoting B-cell responses that are essential for effective viral control. However, as a mediator of inflammation, I L-21 is also involved in the development of HBV-induced liver cirrhosis and exacerbating liver injury. Overall, the current data point to IL-21 as an immunomodulatory cytokine in HBV infection. Immunotherapeutic strategies aimed at optimizing the beneficial effects of IL-21 in HBV infection may prove to be a rigorous challenge in the future, as they should foster the strengths of IL-21 while circumventing potential drawbacks.展开更多
Background Peg-lnterferon-a treatment is expensive and associated with considerable adverse effects, selection of patients with the highest probability of response is essential for clinical practice. The objective of ...Background Peg-lnterferon-a treatment is expensive and associated with considerable adverse effects, selection of patients with the highest probability of response is essential for clinical practice. The objective of this study was to assess the relationship between the gene polymorphisms of interleukin-28 （IL-28）, p21-activated protein kinase 4 （PAK4） and the response to interferon treatment in chronic hepatitis B patients. Methods Two hundred and forty interferon-naive treatment HBeAg seropositive chronic hepatitis B patients were enrolled in the present prospective nested case-control study. Peripheral blood samples were collected, including 92 with favorable response and 148 without response to the interferon treatment. Rs8099917, rs12980602, and rs9676717 SNP was genotyped using matrix assisted laser desorption/ionization time of flight mass spectrometry （MALDI-TOF MS）. Results IL-28 genotype was not associated with response to interferon treatment （OR for GT/GG vs. TT, 0.881 （95% CI 0.388-2.002）; P=0.762; OR for CT/CC vs. TT, 0.902 （95% CI 0.458-1.778）; P=-0.766）. Rs9676717 in PAK4 genotype was independently associated with the response （OR for CT/CC vs. TT, 0.524 （95% CI 0.310-0.888）; P=0.016）. When adjusting for age, gender, smoking, drinking, levels of hepatitis B virus DNA, and alanine aminotransferase （ALT）, rs9676717 genotype TT appeared to be associated with a higher probability of response for interferon treatment （OR, 0.155 （95% CI 0.034-0.700）; P=0.015）. Conclusion Genotype TTfor rs9676717 in PAK4 gene and no drinking may be predictive of the interferon-a treatment success.展开更多
BACKGROUND Thrombopoietin(TPO)is a primary regulator of thrombopoiesis in physiological conditions.TPO,in combination with its specific cytokine receptor c-Mpl,drives platelet production by inducing the proliferation ...BACKGROUND Thrombopoietin(TPO)is a primary regulator of thrombopoiesis in physiological conditions.TPO,in combination with its specific cytokine receptor c-Mpl,drives platelet production by inducing the proliferation and differentiation of megakaryocytes.However,the role of TPO in sepsis is not well determined.The elevated levels of TPO are often accompanied by a decrease of platelet count(PLT)in systemic infected conditions,which is contrary to the view that TPO promotes platelet production under physiological conditions.In addition,whether TPO mediates organ damage in sepsis remains controversial.AIM To explore the relationships between TPO and inflammatory factors,platelet indices,and thrombotic indicators in sepsis.METHODS A total of 90 patients with sepsis diagnosed and treated at the emergency medicine department of The First People’s Hospital of Foshan between January 2020 and March 2021 were enrolled in this study.In addition,110 patients without sepsis who came to the emergency medicine department were included as controls.Clinical and laboratory parameters including age,gender,TPO,blood cell count in peripheral blood,platelet indices,inflammatory factors such as high-sensitivity Creactive protein(hs-CRP),interleukin(IL)-21,and IL-6,organ damage indicators,and thrombotic indicators were collected and analyzed by using various statistical approaches.RESULTS The results showed that the TPO levels were higher in the sepsis group than in controls[86.45(30.55,193.1)vs 12.45(0.64,46.09)pg/mL,P<0.001],but PLT was lower(P<0.001).Multivariable analysis showed that white blood cell count(WBC)[odds ratio(OR)=1.32;95%confidence interval(CI):1.01-1.722;P=0.044],TPO(OR=1.02;95%CI:1.01-1.04;P=0.009),IL-21(OR=1.02;95%CI:1.00-1.03;P=0.019),troponin I(OR=55.20;95%CI:5.69-535.90;P=0.001),and prothrombin time(PT)(OR=2.24;95%CI:1.10-4.55;P=0.027)were independent risk factors associated with sepsis.TPO levels were positively correlated with IL-21,IL-6,hs-CRP,creatinine,D-dimer,PT,activated prothrombin time,international normalized ratio,fibrinogen,WBC count,and neutrophil count,and negatively correlated with PLT,thrombin time,red blood cell count,and hemoglobin concentration(P<0.05).Receiver operating characteristic analysis showed that TPO had fair predictive value in distinguishing septic patients and non-septic patients(the area under the curve:0.788;95%CI:0.723-0.852;P<0.001).With an optimized cutoff value(28.51 pg/mL),TPO had the highest sensitivity(79%)and specificity(65%).CONCLUSION TPO levels are independently associated with sepsis.High TPO levels and low PLT suggest that TPO might be an acute-phase response protein in patients with infection.展开更多
A correct antibody response requires the participation of both B and T lymphocytes and antigen presenting cells. In this review we address the role of follicular helper T lymphocytes(T FH) in this reaction. We shall f...A correct antibody response requires the participation of both B and T lymphocytes and antigen presenting cells. In this review we address the role of follicular helper T lymphocytes(T FH) in this reaction. We shall focus on the regulation of their development and function in health and disease. T FH can be characterized on the basis of their phenotype and the pattern of secretion of cytokines. This fact is useful to study their participation in the generation of antibody deficiency in primary immunodeficiency diseases such as common variable immunodeficiency, X-linked hyper Ig M syndrome orX-linked lymphoproliferative disease. Increased numbers of T FH have been demonstrated in several autoimmune diseases and are thought to play a role in the development of autoantibodies. In chronic viral infections caused by the human immunodeficiency virus, hepatitis B or C virus, increased circulating T FH have been observed, but their role in the protective immune response to these agents is under discussion. Likewise, an important role of T FH in the control of some experimental protozoan infections has been proposed, and it will be important to assess their relevance in order to design effective vaccination strategies.展开更多
Graft versus host disease(GVHD)is a refractory complication of allogeneic hematopoietic stem cell transplantation for the treatment of malignant and non-malignant hematopoietic diseases.Inflammatory cascade responses ...Graft versus host disease(GVHD)is a refractory complication of allogeneic hematopoietic stem cell transplantation for the treatment of malignant and non-malignant hematopoietic diseases.Inflammatory cascade responses and cellular immune reactions are the major factors underlying GVHD pathogenesis.Cells producing the cytokine,interleukin(IL)-21 are crucial players involved in injured tissues in GVHD patients.Besides T helper 17 cells,follicular T helper(Tfh)cells are a new source of IL-21 and play a vital role in GVHD pathogenesis.Tfh cell function is mostly regulated by T-follicular regulatory(Tfr)cells that are also located in the germinal center.This review highlights recent advances in the role of Tfh and Tfr cell function in GVHD pathogenesis.New insights are provided into the potential for clinical application in GVHD prevention and treatment.展开更多
基金Supported by Fondazione Umberto di Mario,Rome,the Broad Medical Research Program Foundation (Grant No. IBD-0154R)and Giuliani SpA,Milan,Italy
文摘In the gut of patients with Crohn's disease and patients with ulcerative colitis,the major forms of inflammatory bowel diseases(IBD) in humans,the tissue-damaging immune response is mediated by an active cross-talk between immune and non-immune cells.Accumulating evidence indicates also that cytokines produced by these cells play a major role in initiating and shaping this pathologic process.One such cytokine seems to be interleukin(IL)-21,a member of the common γ-chainreceptor family.IL-21 is produced in excess in the in-flamed intestine of patients with IBD mostly by activated CD4+ T helper cells co-expressing interferon-γ and follicular T helper cells.Moreover,both in vitro and in vivo studies indicate that excessive IL-21 production leads to the activation of multiple signaling pathways that expand and sustain the ongoing mucosal inflammation.In this article,we review the available data supporting the pathogenic role of IL-21 in IBD.
基金Supported by the Fundamental Research Funds for the Central Universities,No.zdyf2017007Project of Shaanxi Health and Culture Research Center,No.JKWH2019-Z02
文摘BACKGROUND The single nucleotide polymorphisms of interleukin-21(IL-21)gene were confirmed to be related to various diseases,but no studies have examined the possible role of IL-21 single nucleotide polymorphisms(SNPs)(rs907715,rs2221903,and rs12508721)in gastric precancerous lesions.AIM To explore the associations between SNPs of IL-21 gene(rs907715,rs2221903,and rs12508721)and gastric precancerous lesions in a Chinese population.METHODS Three SNPs of IL-21 were genotyped using polymerase chain reaction–ligase detection reaction in 588 cases and 290 healthy controls from May 2013 to December 2016 in northwestern China.Gastric precancerous lesions were confirmed by endoscopic examination and categorized as non-atrophic gastritis,atrophic gastritis,and intestinal metaplasia.Descriptive statistic and logistic regression were used for data analyses.RESULTS IL-21 rs907715 genotype CC and C frequencies were higher in in patients with gastric precancerous lesions than in the controls(OR=1.59,95%CI:1.06-2.38,P=0.013;OR=1.28,95%CI:1.01-2.22,P=0.044,respectively)after adjusting for confounding factors.For SNP rs907715 in intestinal metaplasia patients,significant differences between cases and controls were observed in the frequencies of genotype CC and C(OR=1.92,95%CI:1.24-2.98,P=0.004;OR=1.53,95%CI:1.04-2.24,P=0.028,respectively);for non-atrophic gastritis and atrophic gastritis patients,the CC and C genotypes showed no significant association with risk in all models.No association between either rs2221903 or rs12508721 and gastric precancerous lesions was found in the present study.In the haplotype analysis,the TC haplotype(rs907715 and rs12508721)and TT haplotype(rs2221903 and rs907715)were more frequent in the case group than control group(P<0.05).CONCLUSION Our findings indicate that SNP rs907715 of IL-21 gene is associated with gastric precancerous lesions.The TC haplotype(rs907715 and rs12508721)and TT haplotype(rs2221903 and rs907715)increased the risk of gastric precancerous lesions.If confirmed,these findings will shed light on the etiology of precancerous lesions.
基金the Science and Technology Bureau,No.MS22018007Six Peak Talents in Jiangsu Province,No.YY-177+4 种基金Project of Jiangsu Province Youth Medical Talent Development,No.QNRC2016400 and No.QNRC2016697Project of Nantong Youth Medical Talent Development,No.05Youth Fund of the National Natural Science Foundation of China,No.82000497Youth Fund of the Natural Science Foundation of Jiangsu Province,No.BK20200965Scientific Research Fund of Nantong Health Commission,No.MB2020037.
文摘BACKGROUND Although expression of interleukin(IL)-34 is upregulated in active ulcerative colitis(UC),the molecular function and underlying mechanism are largely unclear.AIM To investigate the function of IL-34 in acute colitis,in a wound healing model and in colitis-associated cancer in IL-34-deficient mice.METHODS Colitis was induced by administration of dextran sodium sulfate(DSS),and carcinogenesis was induced by azoxymethane(AOM).Whether the impact of IL-34 on colitis was dependent on macrophages was validated by depletion of macrophages in a murine model.The association between IL-34 expression and epithelial proliferation was studied in patients with active UC.RESULTS IL-34 deficiency aggravated murine colitis in acute colitis and in wound healing phase.The effect of IL-34 on experimental colitis was not dependent on macrophage differentiation and polarization.IL-34-deficient mice developed more tumors than wild-type mice following administration of AOM and DSS.No significant difference was shown in degree of cellular differentiation in tumors between wild-type and IL-34-deficient mice.IL-34 was dramatically increased in the active UC patients as previously reported.More importantly,expression of IL-34 was positively correlated with epithelial cell proliferation in patients with UC.CONCLUSION IL-34 deficiency exacerbates colonic inflammation and accelerates colitis-associated carcinogenesis in mice.It might be served as a potential therapeutic target in UC.
基金The authors express their sincere thanks to Drs Xiaoyong Zhang and Chris Kafai Li for their critical comments. This work was supported by the Major Science and Technology Special Project of China （2008ZX10002-004, 2012ZX10002-003 and 2011CB946100） and the National Natural Science Foundation of China （81270025）.
文摘I nterleukin （I L）-21, a cytokine produced by activated CD4＋ T cells, has broad pleiotropic actions that affect the functions of a variety of lymphoid cells. The roles of IL-21 in modulating immunity to infections are currently being defined. Notably, IL-21-mediated cellular and humoral immune responses play an important role in determining the outcome of viral infection. This article reviews the current knowledge on the critical role of IL-21 in hepatitis B virus （HBV） infection. As a competent intermediary, IL-21 derived from virus-specific CD4＋ T cells plays key roles in sustaining CD8＋ T cells and promoting B-cell responses that are essential for effective viral control. However, as a mediator of inflammation, I L-21 is also involved in the development of HBV-induced liver cirrhosis and exacerbating liver injury. Overall, the current data point to IL-21 as an immunomodulatory cytokine in HBV infection. Immunotherapeutic strategies aimed at optimizing the beneficial effects of IL-21 in HBV infection may prove to be a rigorous challenge in the future, as they should foster the strengths of IL-21 while circumventing potential drawbacks.
基金This study was supported by grants from the National Natural Science Foundation of China （No. 30972516）, and the Health Department of Hebei Province （No. 20110086 and 20090004）.
文摘Background Peg-lnterferon-a treatment is expensive and associated with considerable adverse effects, selection of patients with the highest probability of response is essential for clinical practice. The objective of this study was to assess the relationship between the gene polymorphisms of interleukin-28 （IL-28）, p21-activated protein kinase 4 （PAK4） and the response to interferon treatment in chronic hepatitis B patients. Methods Two hundred and forty interferon-naive treatment HBeAg seropositive chronic hepatitis B patients were enrolled in the present prospective nested case-control study. Peripheral blood samples were collected, including 92 with favorable response and 148 without response to the interferon treatment. Rs8099917, rs12980602, and rs9676717 SNP was genotyped using matrix assisted laser desorption/ionization time of flight mass spectrometry （MALDI-TOF MS）. Results IL-28 genotype was not associated with response to interferon treatment （OR for GT/GG vs. TT, 0.881 （95% CI 0.388-2.002）; P=0.762; OR for CT/CC vs. TT, 0.902 （95% CI 0.458-1.778）; P=-0.766）. Rs9676717 in PAK4 genotype was independently associated with the response （OR for CT/CC vs. TT, 0.524 （95% CI 0.310-0.888）; P=0.016）. When adjusting for age, gender, smoking, drinking, levels of hepatitis B virus DNA, and alanine aminotransferase （ALT）, rs9676717 genotype TT appeared to be associated with a higher probability of response for interferon treatment （OR, 0.155 （95% CI 0.034-0.700）; P=0.015）. Conclusion Genotype TTfor rs9676717 in PAK4 gene and no drinking may be predictive of the interferon-a treatment success.
基金Supported by the Guangdong Province Medical Science and Technology Research Foundation,No.B2014377the Medical Scientific Research Project of Foshan,No.20190036.
文摘BACKGROUND Thrombopoietin(TPO)is a primary regulator of thrombopoiesis in physiological conditions.TPO,in combination with its specific cytokine receptor c-Mpl,drives platelet production by inducing the proliferation and differentiation of megakaryocytes.However,the role of TPO in sepsis is not well determined.The elevated levels of TPO are often accompanied by a decrease of platelet count(PLT)in systemic infected conditions,which is contrary to the view that TPO promotes platelet production under physiological conditions.In addition,whether TPO mediates organ damage in sepsis remains controversial.AIM To explore the relationships between TPO and inflammatory factors,platelet indices,and thrombotic indicators in sepsis.METHODS A total of 90 patients with sepsis diagnosed and treated at the emergency medicine department of The First People’s Hospital of Foshan between January 2020 and March 2021 were enrolled in this study.In addition,110 patients without sepsis who came to the emergency medicine department were included as controls.Clinical and laboratory parameters including age,gender,TPO,blood cell count in peripheral blood,platelet indices,inflammatory factors such as high-sensitivity Creactive protein(hs-CRP),interleukin(IL)-21,and IL-6,organ damage indicators,and thrombotic indicators were collected and analyzed by using various statistical approaches.RESULTS The results showed that the TPO levels were higher in the sepsis group than in controls[86.45(30.55,193.1)vs 12.45(0.64,46.09)pg/mL,P<0.001],but PLT was lower(P<0.001).Multivariable analysis showed that white blood cell count(WBC)[odds ratio(OR)=1.32;95%confidence interval(CI):1.01-1.722;P=0.044],TPO(OR=1.02;95%CI:1.01-1.04;P=0.009),IL-21(OR=1.02;95%CI:1.00-1.03;P=0.019),troponin I(OR=55.20;95%CI:5.69-535.90;P=0.001),and prothrombin time(PT)(OR=2.24;95%CI:1.10-4.55;P=0.027)were independent risk factors associated with sepsis.TPO levels were positively correlated with IL-21,IL-6,hs-CRP,creatinine,D-dimer,PT,activated prothrombin time,international normalized ratio,fibrinogen,WBC count,and neutrophil count,and negatively correlated with PLT,thrombin time,red blood cell count,and hemoglobin concentration(P<0.05).Receiver operating characteristic analysis showed that TPO had fair predictive value in distinguishing septic patients and non-septic patients(the area under the curve:0.788;95%CI:0.723-0.852;P<0.001).With an optimized cutoff value(28.51 pg/mL),TPO had the highest sensitivity(79%)and specificity(65%).CONCLUSION TPO levels are independently associated with sepsis.High TPO levels and low PLT suggest that TPO might be an acute-phase response protein in patients with infection.
基金Supported by Consejo Nacional de Investigaciones Científicas y Técnicas,CONICET,PIP Nos.0032 and 11220120100619CO
文摘A correct antibody response requires the participation of both B and T lymphocytes and antigen presenting cells. In this review we address the role of follicular helper T lymphocytes(T FH) in this reaction. We shall focus on the regulation of their development and function in health and disease. T FH can be characterized on the basis of their phenotype and the pattern of secretion of cytokines. This fact is useful to study their participation in the generation of antibody deficiency in primary immunodeficiency diseases such as common variable immunodeficiency, X-linked hyper Ig M syndrome orX-linked lymphoproliferative disease. Increased numbers of T FH have been demonstrated in several autoimmune diseases and are thought to play a role in the development of autoantibodies. In chronic viral infections caused by the human immunodeficiency virus, hepatitis B or C virus, increased circulating T FH have been observed, but their role in the protective immune response to these agents is under discussion. Likewise, an important role of T FH in the control of some experimental protozoan infections has been proposed, and it will be important to assess their relevance in order to design effective vaccination strategies.
基金This work was in part supported by the National Natural Science Foundation of China(81373156,81570587,81401324,81671611)Science and Technology Planning Project of Guangdong Province(2016A020215048,2014A030308005)+1 种基金Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology(2013A061401007)Guangdong Provincial International Cooperation Base of Science and Technology(Organ Transplantation)(2015B050501002),China.
文摘Graft versus host disease(GVHD)is a refractory complication of allogeneic hematopoietic stem cell transplantation for the treatment of malignant and non-malignant hematopoietic diseases.Inflammatory cascade responses and cellular immune reactions are the major factors underlying GVHD pathogenesis.Cells producing the cytokine,interleukin(IL)-21 are crucial players involved in injured tissues in GVHD patients.Besides T helper 17 cells,follicular T helper(Tfh)cells are a new source of IL-21 and play a vital role in GVHD pathogenesis.Tfh cell function is mostly regulated by T-follicular regulatory(Tfr)cells that are also located in the germinal center.This review highlights recent advances in the role of Tfh and Tfr cell function in GVHD pathogenesis.New insights are provided into the potential for clinical application in GVHD prevention and treatment.
