Role of innate lymphoid cells in chronic colitis during anti-IL-17A therapyopen access
- Authors
- Park, Chan Hyuk; Lee, A-reum; Ahn, Sang Bong; Eun, Chang Soo; Han, Dong Soo
- Issue Date
- Jan-2020
- Publisher
- NATURE PUBLISHING GROUP
- Citation
- SCIENTIFIC REPORTS, v.10, no.1, pp.1 - 11
- Indexed
- SCIE
SCOPUS
- Journal Title
- SCIENTIFIC REPORTS
- Volume
- 10
- Number
- 1
- Start Page
- 1
- End Page
- 11
- URI
- https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/11511
- DOI
- 10.1038/s41598-019-57233-w
- ISSN
- 2045-2322
- Abstract
- 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 ROR gamma t(+) 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 ROR gamma t(+) 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-ROR gamma t(+) 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-ROR gamma t(+) 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, ROR gamma t(+) 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 ROR gamma t(+) ILCs in chronic colitis, thereby upregulating IL-22 and worsening the clinical outcomes of patients with Crohn's disease.
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