Essential role of IFN-γ in T cell-associated intestinal inflammation

Yoshihiro Eriguchi, Kiminori Nakamura, Yuki Yokoi, Rina Sugimoto, Shuichiro Takahashi, Daigo Hashimoto, Takanori Teshima, Tokiyoshi Ayabe, Michael E. Selsted, André J. Ouellette

研究成果: ジャーナルへの寄稿記事

4 引用 (Scopus)

抜粋

Paneth cells contribute to small intestinal homeostasis by secreting antimicrobial peptides and constituting the intestinal stem cell (ISC) niche. Certain T cell-mediated enteropathies are characterized by extensive Paneth cell depletion coincident with mucosal destruction and dysbiosis. In this study, mechanisms of intestinal crypt injury have been investigated by characterizing responses of mouse intestinal organoids (enteroids) in coculture with mouse T lymphocytes. Activated T cells induced enteroid damage, reduced Paneth cell and Lgr5+ ISC mRNA levels, and induced Paneth cell death through a caspase-3/7-dependent mechanism. IFN-γ mediated these effects, because IFN-γ receptor-null enteroids were unaffected by activated T cells. In mice, administration of IFN-γ induced enteropathy with crypt hyperplasia, villus shortening, Paneth cell depletion, and modified ISC marker expression. IFN-γ exacerbated radiation enteritis, which was ameliorated by treatment with a selective JAK1/2 inhibitor. Thus, IFN-γ induced Paneth cell death and impaired regeneration of small intestinal epithelium in vivo, suggesting that IFN-γ may be a useful target for treating defective mucosal regeneration in enteric inflammation.

元の言語英語
ジャーナルJCI Insight
3
発行部数18
DOI
出版物ステータス出版済み - 9 20 2018
外部発表Yes

    フィンガープリント

All Science Journal Classification (ASJC) codes

  • Medicine(all)

これを引用

Eriguchi, Y., Nakamura, K., Yokoi, Y., Sugimoto, R., Takahashi, S., Hashimoto, D., ... Ouellette, A. J. (2018). Essential role of IFN-γ in T cell-associated intestinal inflammation. JCI Insight, 3(18). https://doi.org/10.1172/jci.insight.121886