美国国立卫生研究院John J. O’Shea、Yuka Kanno等研究人员合作发现，microRNA-221和-222作为白细胞介素23下游的负反馈调节因子来调节肠道炎症性Th17细胞反应 。2021年3月2日，国际知名学术期刊《免疫》在线发表了这一成果。

microRNA是免疫反应的重要调节分子。研究人员发现，miR-221和miR-222可调节肠道Th17细胞反应。miR-221和miR-222的表达由促炎性细胞因子诱导，并被细胞因子TGF-β抑制。miR-221和miR-222的分子靶标包括Maf和Il23r，而miR-221和miR-222表达的缺失可将肠道Th17细胞的转录组谱转变为促炎信号。尽管为维持健康小鼠的肠道Th17细胞稳态耐受了miR-221和miR-222的丧失，但缺少miR-221和miR-222的Th17细胞对IL-23的反应更有效。miR-221和miR-222的全身性和T细胞特异性缺失都使小鼠易于发生粘膜屏障损伤。

总体而言，这些发现表明，miR-221和miR-222是肠道Th17细胞应答的组成部分，可在IL-23刺激后被诱导来限制促炎反应的强度。 

附：英文原文

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

Author: Yohei Mikami, Rachael L. Philips, Giuseppe Sciumè, Franziska Petermann, Franoise 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

Issue&Volume: 2021-03-02

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

DOI: 10.1016/j.immuni.2021.02.015

Source: https://www.cell.com/immunity/fulltext/S1074-7613(21)00081-9