@article{8621beddde60493dbdb557f1c1442945,
title = "MicroRNA-221 and -222 modulate intestinal inflammatory Th17 cell response as negative feedback regulators downstream of interleukin-23",
abstract = "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.",
keywords = "IL23r, Maf, Th17, helper T cells, intestine, miR-221, miR-222, miRNA, mucosal barrier damage, negative feedback",
author = "Yohei Mikami and Philips, {Rachael L.} and Giuseppe Scium{\`e} and Franziska Petermann and Fran{\c c}oise Meylan and Hiroyuki Nagashima and Chen Yao and Davis, {Fred P.} and Brooks, {Stephen R.} and Sun, {Hong Wei} and Hayato Takahashi and Poholek, {Amanda C.} and Shih, {Han Yu} and Behdad Afzali and Muljo, {Stefan A.} and Markus Hafner and Yuka Kanno and O'Shea, {John J.}",
note = "Funding Information: We thank J. Simone, J. Lay, K. Tinsley (NIAMS) for flow cytometry; G. Gutierrez-Cruz, S. Dell{\textquoteright}Orso, F. Naz (NIAMS) for deep sequencing; K. Jiang and Dimitrios Anastasakis (NIAMS) for bioinformatics support; Ivan Fuss (NIAID) for histopathologic scoring; and the NIAMS LACU staff and Y. Morimoto (NIAMS) for their technical support to handle mice. We thank Vanja Lazarevic (NCI) and Mark Ansel (UCSF) for critical reading, the members of the O{\textquoteright}Shea laboratory for helpful discussions, and Tomoya Kanno for graphics. This study utilized the high-performance computational capabilities of the Biowulf Linux cluster at the NIH. This work was supported by the Intramural Research Programs of NIAMS and NIAID . Y.M. was supported by Japan Society for the Promotion of Science (JSPS) KAKENHI Grant-in-Aid (B) 20H03666 and Japanese Researcher Fellowships at NIH . R.L.P. was supported by a Postdoctoral Research Associate (PRAT) fellowship from the National Institute of General Medical Sciences (NIGMS), award number 1Fi2GM137942-01 . Funding Information: We thank J. Simone, J. Lay, K. Tinsley (NIAMS) for flow cytometry; G. Gutierrez-Cruz, S. Dell'Orso, F. Naz (NIAMS) for deep sequencing; K. Jiang and Dimitrios Anastasakis (NIAMS) for bioinformatics support; Ivan Fuss (NIAID) for histopathologic scoring; and the NIAMS LACU staff and Y. Morimoto (NIAMS) for their technical support to handle mice. We thank Vanja Lazarevic (NCI) and Mark Ansel (UCSF) for critical reading, the members of the O'Shea laboratory for helpful discussions, and Tomoya Kanno for graphics. This study utilized the high-performance computational capabilities of the Biowulf Linux cluster at the NIH. This work was supported by the Intramural Research Programs of NIAMS and NIAID. Y.M. was supported by Japan Society for the Promotion of Science (JSPS) KAKENHI Grant-in-Aid (B) 20H03666 and Japanese Researcher Fellowships at NIH. R.L.P. was supported by a Postdoctoral Research Associate (PRAT) fellowship from the National Institute of General Medical Sciences (NIGMS), award number 1Fi2GM137942-01. Conceptualization, Y.M. and J.J.O.; methodology, Y.M. and H.T.; software, Y.M. F.P.D. H.-W.S. and S.R.B.; validation, Y.M. R.L.P. and S.R.B.; formal analysis, Y.M. R.L.P. S.R.B. and F.P.D.; investigation, Y.M. R.L.P. G.S. F.P. H.N. C.Y. F.M. A.C.P. H.-Y.S. B.A. and Y.K.; writing, Y.M. R.L.P. Y.K. and J.J.O.; visualization, Y.M. R.L.P. and S.R.B.; supervision, S.A.M. M.H. Y.K. and J.J.O.; funding acquisition, M.H. S.A.M. and J.J.O. The authors declare no competing financial interests. J.J.O. is a member of the advisory board of Immunity. Publisher Copyright: {\textcopyright} 2021",
year = "2021",
month = mar,
day = "9",
doi = "10.1016/j.immuni.2021.02.015",
language = "English",
volume = "54",
pages = "514--525.e6",
journal = "Immunity",
issn = "1074-7613",
publisher = "Cell Press",
number = "3",
}
