机构地区:[1]Department of Gastroenterology and Hepatology,Jiangxi Provincial People’s Hospital,Nanchang 330006,Jiangxi Province,China [2]Jiangxi Medical College,Nanchang University,Nanchang 330006,Jiangxi Province,China [3]Department of Microbiology and Immunology,Shenzhen University Health Science Center,Shenzhen 518000,Guangdong Province,China [4]Department of Pharmaceutical/Medicinal Chemistry,Institute of Pharmacy,Friedrich Schiller University,Jena 07743,Germany
出 处:《World Journal of Gastroenterology》2019年第20期2473-2488,共16页世界胃肠病学杂志(英文版)
基 金:Supported by Key R&D Plan of Science and Technology Department of Jiangxi Province,No.20171BBG70087
摘 要:BACKGROUND It is challenging to distinguish intestinal tuberculosis from Crohn’s disease due to dynamic changes in epidemiology and similar clinical characteristics. Recent studies have shown that polymorphisms in genes involved in the interleukin (IL)- 23/IL-17 axis may affect intestinal mucosal immunity by affecting the differentiation of Th17 cells. AIM To investigate the specific single-nucleotide polymorphisms (SNPs) in genes involved in the IL-23/IL-17 axis and possible pathways that affect susceptibility to intestinal tuberculosis and Crohn's disease. METHODS We analysed 133 patients with intestinal tuberculosis, 128 with Crohn’s disease, and 500 normal controls. DNA was extracted from paraffin-embedded specimens or whole blood. Four SNPs in the IL23/Th17 axis (IL22 rs2227473, IL1β rs1143627, TGFβ rs4803455, and IL17 rs8193036) were genotyped with TaqMan assays. The transcriptional activity levels of different genotypes of rs2227473 were detected by dual luciferase reporter gene assay. The expression of IL-22R1 in different intestinal diseases was detected by immunohistochemistry. RESULTS The A allele frequency of rs2227473 (P = 0.030, odds ratio = 0.60, 95% confidence interval: 0.37-0.95) showed an abnormal distribution between intestinal tuberculosis and healthy controls. The presence of the A allele was associated with a higher IL-22 transcriptional activity (P < 0.05). In addition, IL-22R1 was expressed in intestinal lymphoid tissues, especially under conditions of intestinal tuberculosis, and highly expressed in macrophage-derived Langhans giant cells. The results of immunohistochemistry showed that the expression of IL-22R1 in patients with Crohn's disease and intestinal tuberculosis was significantly higher than that in patients with intestinal polyps and colon cancer (P < 0.01). CONCLUSION High IL-22 expression seems to be a protective factor for intestinal tuberculosis. IL-22R1 is expressed in Langhans giant cells, suggesting that the IL-22/IL-22R1 system links adaptive and innate immunity.BACKGROUND It is challenging to distinguish intestinal tuberculosis from Crohn’s disease due to dynamic changes in epidemiology and similar clinical characteristics. Recent studies have shown that polymorphisms in genes involved in the interleukin(IL)-23/IL-17 axis may affect intestinal mucosal immunity by affecting the differentiation of Th17 cells.AIM To investigate the specific single-nucleotide polymorphisms(SNPs) in genes involved in the IL-23/IL-17 axis and possible pathways that affect susceptibility to intestinal tuberculosis and Crohn’s disease.METHODS We analysed 133 patients with intestinal tuberculosis, 128 with Crohn’s disease,and 500 normal controls. DNA was extracted from paraffin-embedded specimens or whole blood. Four SNPs in the IL23/Th17 axis(IL22 rs2227473, IL1β rs1143627,TGFβ rs4803455, and IL17 rs8193036) were genotyped with TaqMan assays. The transcriptional activity levels of different genotypes of rs2227473 were detected by dual luciferase reporter gene assay. The expression of IL-22 R1 in different intestinal diseases was detected by immunohistochemistry.RESULTSThe A allele frequency of rs2227473(P = 0.030, odds ratio = 0.60, 95% confidence interval: 0.37-0.95) showed an abnormal distribution between intestinal tuberculosis and healthy controls. The presence of the A allele was associated with a higher IL-22 transcriptional activity(P < 0.05). In addition, IL-22 R1 was expressed in intestinal lymphoid tissues, especially under conditions of intestinal tuberculosis, and highly expressed in macrophage-derived Langhans giant cells.The results of immunohistochemistry showed that the expression of IL-22 R1 in patients with Crohn’s disease and intestinal tuberculosis was significantly higher than that in patients with intestinal polyps and colon cancer(P < 0.01).CONCLUSION High IL-22 expression seems to be a protective factor for intestinal tuberculosis.IL-22 R1 is expressed in Langhans giant cells, suggesting that the IL-22/IL-22 R1 system links adaptive and innate immunity.
关 键 词:Crohn's disease INTESTINAL tuberculosis Single-nucleotide polymorphism INTERLEUKIN-22 INTERLEUKIN-22 RECEPTOR 1 Multinucleated giant cells
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