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
The tumor microenvironment is characterized by an immunosuppressive state.Although PD-1/PD-L1 blockade therapy activates the immune system against tumors,it has limited long-term efficacy,prompting the development of ...The tumor microenvironment is characterized by an immunosuppressive state.Although PD-1/PD-L1 blockade therapy activates the immune system against tumors,it has limited long-term efficacy,prompting the development of combination therapies with targeted treatments to improve cancer treatment outcomes.Recent advancements have revitalized interest in using attenuated Salmonella strains as cancer therapeutics that target tumors,induce immune responses,and promote tumor cell death,although complete tumor suppression remains challenging.We aimed to induce antitumor effects by activating the suppressed immune system within the tumor microenvironment using Salmonella-mediated secretion of interleukin-21(IL-21).We used the tumor-targeting ability of Salmonella and its flagellar type-3 secretion system(FT3SS)to induce the secretion of IL-21 into the tumor microenvironment via the flagellar system and evaluated the local immune response.We also evaluated the efficacy of combining Salmonella-mediated IL-21 delivery and anti-PD-L1 therapy in a mouse model.IL-21 secretion promoted the recruitment of CD4+and CD8+T cells and enhanced the expression of cytotoxicity-related molecules.Tumor-bearing mice treated with the combination therapy with anti-PD-L1 antibodies showed improved survival rates and enhanced tumor growth inhibition.This study demonstrates the tumor-targeting capability and in vivo safety of Salmonella,highlighting its potential as a powerful cancer therapy platform.展开更多
目的探讨过敏性紫癜(henoch-Schonlein syndrome,HSP)患儿发生肾损害与血清B淋巴细胞活化因子(B lymphocyte activating factor,BAFF)、白细胞介素21(interleukin-21,IL-21)表达的相关性,以期进一步明确儿童HSPN的病因、发病机制,为临...目的探讨过敏性紫癜(henoch-Schonlein syndrome,HSP)患儿发生肾损害与血清B淋巴细胞活化因子(B lymphocyte activating factor,BAFF)、白细胞介素21(interleukin-21,IL-21)表达的相关性,以期进一步明确儿童HSPN的病因、发病机制,为临床诊治提供依据。方法选取2021年1月—2021年12月在该院住院的过敏性紫癜患儿,根据是否发生肾损害分为紫癜性肾炎组(HSPN组)及过敏性紫癜组(HSP组),选择同时期在该院门诊体检的健康儿童15例,检测各组患儿血清BAFF、IL-21水平,并收集临床一般料以及24 h尿蛋白定量(24 h urinary protein,24 h UTP)、血肌酐(creatinine,Scr)、尿素氮(creatinine,BUN)、尿酸(uric acid,UA)等,并估算患儿肾小球滤过率(eGFR)。比较各组血清BAFF、IL-21表达水平,分析与HSPN发病及中医证型的相关性。结果(1)一般情况:男66例,女39例,男女比例为1.69∶1,3组间年龄及性别比较均差异无统计学意义(P>0.05)。(2)HSP组、HSPN组BAFF、IL-21水平高于健康对照组(P<0.01);HSPN组BAFF、IL-21水平高于HSP组(P<0.01)。患儿血清IL-21、BAFF水平呈正相关(P<0.01)。(3)HSPN患儿BAFF表达水平与Scr及BUN水平呈正相关,与eGFR呈负相关(P<0.05);与24 h UTP、UA、是否腹痛及关节痛无相关性(P>0.05)。HSPN患儿IL-21表达水平与eGFR呈负相关(P<0.05);与24 h UTP、Scr、BUN、UA、是否腹痛及关节痛无相关性(P>0.05)。(4)BAFF、IL-21水平是HSP患儿发生肾损害的危险因素(P<0.05)。(5)阴虚夹瘀证、气阴两虚夹瘀证BAFF、IL-21水平高于风热伤络证、血热夹瘀证(P<0.05)。结论HSPN患儿血清BAFF、IL-21水平明显增高,并与疾病严重程度呈正相关;BAFF、IL-21是HSP患儿发生肾损害的危险因素;阴虚夹瘀证、气阴两虚夹瘀证BAFF、IL-21表达水平明显增高。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 BK21 FOUR Program by Chungnam National University Research Grant,2025supported by National Research Foundation of Korea grants funded by the Korean government(NRF-2022R1A2C1009875 and RS-2018NR056534,Korea)+2 种基金by the Korea Health Technology R&D Project through the Korea Health Industry Development Institute(KHIDI)funded by the Ministry of Health and Welfare,Republic of Korea(HR20C0025,Korea)supported by NRF-RS202300243742(Korea).Graphical abstract image was created using BioRender.
文摘The tumor microenvironment is characterized by an immunosuppressive state.Although PD-1/PD-L1 blockade therapy activates the immune system against tumors,it has limited long-term efficacy,prompting the development of combination therapies with targeted treatments to improve cancer treatment outcomes.Recent advancements have revitalized interest in using attenuated Salmonella strains as cancer therapeutics that target tumors,induce immune responses,and promote tumor cell death,although complete tumor suppression remains challenging.We aimed to induce antitumor effects by activating the suppressed immune system within the tumor microenvironment using Salmonella-mediated secretion of interleukin-21(IL-21).We used the tumor-targeting ability of Salmonella and its flagellar type-3 secretion system(FT3SS)to induce the secretion of IL-21 into the tumor microenvironment via the flagellar system and evaluated the local immune response.We also evaluated the efficacy of combining Salmonella-mediated IL-21 delivery and anti-PD-L1 therapy in a mouse model.IL-21 secretion promoted the recruitment of CD4+and CD8+T cells and enhanced the expression of cytotoxicity-related molecules.Tumor-bearing mice treated with the combination therapy with anti-PD-L1 antibodies showed improved survival rates and enhanced tumor growth inhibition.This study demonstrates the tumor-targeting capability and in vivo safety of Salmonella,highlighting its potential as a powerful cancer therapy platform.
文摘目的探讨过敏性紫癜(henoch-Schonlein syndrome,HSP)患儿发生肾损害与血清B淋巴细胞活化因子(B lymphocyte activating factor,BAFF)、白细胞介素21(interleukin-21,IL-21)表达的相关性,以期进一步明确儿童HSPN的病因、发病机制,为临床诊治提供依据。方法选取2021年1月—2021年12月在该院住院的过敏性紫癜患儿,根据是否发生肾损害分为紫癜性肾炎组(HSPN组)及过敏性紫癜组(HSP组),选择同时期在该院门诊体检的健康儿童15例,检测各组患儿血清BAFF、IL-21水平,并收集临床一般料以及24 h尿蛋白定量(24 h urinary protein,24 h UTP)、血肌酐(creatinine,Scr)、尿素氮(creatinine,BUN)、尿酸(uric acid,UA)等,并估算患儿肾小球滤过率(eGFR)。比较各组血清BAFF、IL-21表达水平,分析与HSPN发病及中医证型的相关性。结果(1)一般情况:男66例,女39例,男女比例为1.69∶1,3组间年龄及性别比较均差异无统计学意义(P>0.05)。(2)HSP组、HSPN组BAFF、IL-21水平高于健康对照组(P<0.01);HSPN组BAFF、IL-21水平高于HSP组(P<0.01)。患儿血清IL-21、BAFF水平呈正相关(P<0.01)。(3)HSPN患儿BAFF表达水平与Scr及BUN水平呈正相关,与eGFR呈负相关(P<0.05);与24 h UTP、UA、是否腹痛及关节痛无相关性(P>0.05)。HSPN患儿IL-21表达水平与eGFR呈负相关(P<0.05);与24 h UTP、Scr、BUN、UA、是否腹痛及关节痛无相关性(P>0.05)。(4)BAFF、IL-21水平是HSP患儿发生肾损害的危险因素(P<0.05)。(5)阴虚夹瘀证、气阴两虚夹瘀证BAFF、IL-21水平高于风热伤络证、血热夹瘀证(P<0.05)。结论HSPN患儿血清BAFF、IL-21水平明显增高,并与疾病严重程度呈正相关;BAFF、IL-21是HSP患儿发生肾损害的危险因素;阴虚夹瘀证、气阴两虚夹瘀证BAFF、IL-21表达水平明显增高。
