MicroRNA-221 and -222 modulate intestinal inflammatory Th17 cell response as negative feedback regulators downstream of interleukin-23

Yohei Mikami, Rachael L. Philips, Giuseppe Sciumè, Franziska Petermann, Françoise Meylan, Hiroyuki Nagashima, Chen Yao, Fred P. Davis, Stephen R. Brooks, Hong Wei Sun, Hayato Takahashi, Amanda C. Poholek, Han Yu Shih, Behdad Afzali, Stefan A. Muljo, Markus Hafner, Yuka Kanno, John J. O'Shea

研究成果: Article査読

6 被引用数 (Scopus)

抄録

MicroRNAs are important regulators of immune responses. Here, we show miR-221 and miR-222 modulate the intestinal Th17 cell response. Expression of miR-221 and miR-222 was induced by proinflammatory cytokines and repressed by the cytokine TGF-β. Molecular targets of miR-221 and miR-222 included Maf and Il23r, and loss of miR-221 and miR-222 expression shifted the transcriptomic spectrum of intestinal Th17 cells to a proinflammatory signature. Although the loss of miR-221 and miR-222 was tolerated for maintaining intestinal Th17 cell homeostasis in healthy mice, Th17 cells lacking miR-221 and miR-222 expanded more efficiently in response to IL-23. Both global and T cell-specific deletion of miR-221 and miR-222 rendered mice prone to mucosal barrier damage. Collectively, these findings demonstrate that miR-221 and miR-222 are an integral part of intestinal Th17 cell response that are induced after IL-23 stimulation to constrain the magnitude of proinflammatory response.

本文言語English
ページ(範囲)514-525.e6
ジャーナルImmunity
54
3
DOI
出版ステータスPublished - 2021 3月 9
外部発表はい

ASJC Scopus subject areas

  • 免疫アレルギー学
  • 免疫学
  • 感染症

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