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
Celiac disease (CD), an enteropathy caused by dietary gluten in genetically susceptible individuals, is histologically characterized by villous atrophy, crypt cell hyperplasia, and increased number of intra-epithelial...Celiac disease (CD), an enteropathy caused by dietary gluten in genetically susceptible individuals, is histologically characterized by villous atrophy, crypt cell hyperplasia, and increased number of intra-epithelial lymphocytes. The nature of CD pathogenesis remains unclear, but recent evidence indicates that both innate and adaptive immune responses are necessary for the phenotypic expression and pathologic changes characteristic of CD. Extensive studies of molecules produced by immune cells in the gut of CD patients have led to identification of two cytokines, namely interleukin (IL)-15 and IL-21, which are thought to play a major role in orchestrating the mucosal inflammatory response in CD. Here we review the current knowledge of the expression and function of IL-15 and IL-21 in CD.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
Morphological alterations in dendritic spines have been linked to changes in functional communication between neurons that affect learning and memory.Kinesin-4 KIF21A helps organize the microtubule-actin network at th...Morphological alterations in dendritic spines have been linked to changes in functional communication between neurons that affect learning and memory.Kinesin-4 KIF21A helps organize the microtubule-actin network at the cell cortex by interacting with KANK1;however,whether KIF21A modulates dendritic structure and function in neurons remains unknown.In this study,we found that KIF21A was distributed in a subset of dendritic spines,and that these KIF21A-positive spines were larger and more structurally plastic than KIF21A-negative spines.Furthermore,the interaction between KIF21A and KANK1 was found to be critical for dendritic spine morphogenesis and synaptic plasticity.Knockdown of either KIF21A or KANK1 inhibited dendritic spine morphogenesis and dendritic branching,and these deficits were fully rescued by coexpressing full-length KIF21A or KANK1,but not by proteins with mutations disrupting direct binding between KIF21A and KANK1 or binding between KANK1 and talin1.Knocking down KIF21A in the hippocampus of rats inhibited the amplitudes of long-term potentiation induced by high-frequency stimulation and negatively impacted the animals’cognitive abilities.Taken together,our findings demonstrate the function of KIF21A in modulating spine morphology and provide insight into its role in synaptic function.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
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.
文摘Celiac disease (CD), an enteropathy caused by dietary gluten in genetically susceptible individuals, is histologically characterized by villous atrophy, crypt cell hyperplasia, and increased number of intra-epithelial lymphocytes. The nature of CD pathogenesis remains unclear, but recent evidence indicates that both innate and adaptive immune responses are necessary for the phenotypic expression and pathologic changes characteristic of CD. Extensive studies of molecules produced by immune cells in the gut of CD patients have led to identification of two cytokines, namely interleukin (IL)-15 and IL-21, which are thought to play a major role in orchestrating the mucosal inflammatory response in CD. Here we review the current knowledge of the expression and function of IL-15 and IL-21 in CD.
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supported by the National Key Research and Development Program of China,No.2021ZD0202503(to AHT)the National Natural Science Foundation of China,Nos.31872759(to AHT)and 32070707(to CF)+1 种基金Shenzhen Science and Technology Program,No.RCJC20210609104333007(to ZW)Shenzhen-Hong Kong Institute of Brain Science,Shenzhen Fundamental Research Institutions,No.2021SHIBS0002(to ZW).
文摘Morphological alterations in dendritic spines have been linked to changes in functional communication between neurons that affect learning and memory.Kinesin-4 KIF21A helps organize the microtubule-actin network at the cell cortex by interacting with KANK1;however,whether KIF21A modulates dendritic structure and function in neurons remains unknown.In this study,we found that KIF21A was distributed in a subset of dendritic spines,and that these KIF21A-positive spines were larger and more structurally plastic than KIF21A-negative spines.Furthermore,the interaction between KIF21A and KANK1 was found to be critical for dendritic spine morphogenesis and synaptic plasticity.Knockdown of either KIF21A or KANK1 inhibited dendritic spine morphogenesis and dendritic branching,and these deficits were fully rescued by coexpressing full-length KIF21A or KANK1,but not by proteins with mutations disrupting direct binding between KIF21A and KANK1 or binding between KANK1 and talin1.Knocking down KIF21A in the hippocampus of rats inhibited the amplitudes of long-term potentiation induced by high-frequency stimulation and negatively impacted the animals’cognitive abilities.Taken together,our findings demonstrate the function of KIF21A in modulating spine morphology and provide insight into its role in synaptic function.
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.
