文章基本信息

标题：Role of innate lymphoid cells in chronic colitis during anti-IL-17A therapy
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作者：Chan Hyuk Park ; A-reum Lee ; Sang Bong Ahn 等
期刊名称：Scientific Reports
电子版ISSN：2045-2322
出版年度：2020
卷号：10
期号：1
页码：1-11
DOI：10.1038/s41598-019-57233-w
出版社：Springer Nature
摘要：IL-17A is an important cytokine in intestinal inflammation. However, anti-IL-17A therapy does not improve clinical outcomes in patients with Crohn's disease. We aimed to evaluate the role of RORγt + innate lymphoid cells (ILCs) in murine colitis models in the absence of IL-17A. An acute colitis model was induced with either dextran sulfate sodium (DSS) or trinitrobenzenesulfonic acid (TNBS) and a chronic colitis model was induced by CD4 + CD45RB hi T cell transfer from either wild-type C57BL/6 or Il17a -/- mice. An anti-IL-17A antibody, secukinumab, was also used to inhibit IL-17A function in the colitis model. Flow cytometry was performed to analyze the population of RORγt + ILCs in the colonic lamina propria of mice with chronic colitis. Acute intestinal inflammation due to DSS and TNBS was attenuated in IL-17A knockout mice, whereas chronic colitis was not relieved by T cell transfer from Il17a -/- mice (% of original body weight: wild-type mice vs. Il17a -/- mice, 81.9% vs. 82.2%; P = 0.922). However, the mean proportion of Lin - RORγt + lymphocytes was higher after T cell transfer from Il17a -/- mice than that after T cell transfer from wild-type mice (28.8% vs. 18.5%). The proportion of Lin - RORγt + was also increased in Rag2 -/- mice that received T cell transfer from wild-type mice when anti-IL-17A antibody was administered (31.7%). Additionally, Il6 and Il22 tended to be highly expressed after T cell transfer from Il17a -/- mice. In conclusion, RORγt + ILCs may have an important role in the pathogenesis of chronic colitis in the absence of IL-17A. Blocking the function of IL-17A may upregulate Il6 and recruit RORγt + ILCs in chronic colitis, thereby upregulating IL-22 and worsening the clinical outcomes of patients with Crohn's disease.