Interleukin-17D regulates group 3 innate lymphoid cell function through its receptor CD93.
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| Abstract |
The interleukin (IL)-17 family, consisting of six members, promotes host defense but can in some context promote the development of autoimmune disease. Here, we examined the role of IL-17D, a poorly understood member in the IL-17 family. IL-17D was expressed primarily by colonic epithelial cells. Il17d-/- mice were more susceptible to acute colitis, bacterial infection and experimentally induced colon cancer than their wildtype counterparts. Il17d deficiency impaired IL-22 production by group 3 innate lymphoid cells (ILC3s) and reduced expression of IL-22-dependent antimicrobial peptides, RegIIIβ and RegIIIγ, in colon tissue at steady state and in colitis; this was associated with changes in microbial composition and dysbiosis. Protein purification studies revealed that IL-17D bound not canonical IL-17 receptors, but rather CD93, a glycoprotein expressed on mature ILC3s. Mice lacking Cd93 in ILC3s exhibited impaired IL-22 production and aggravated colonic inflammation in experimental colitis. Thus, an IL-17D-CD93 axis regulates ILC3 function to preserve intestinal homeostasis.
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| Authors | Jinling Huang, Hae-Youn Lee, Xiaohong Zhao, Jinyi Han, Yang Su, Qinli Sun, Jing Shao, Jiwan Ge, Yuxi Zhao, Xue Bai, Yi He, Xinquan Wang, Xiaohu Wang, Chen Dong |
| Journal | Immunity (Immunity) Vol. 54 Issue 4 Pg. 673-686.e4 (04 13 2021) ISSN: 1097-4180 [Electronic] United States |
| PMID | 33852831 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
| Copyright | Copyright © 2021 Elsevier Inc. All rights reserved. |
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