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MicroRNA-142 critically regulates group 2 innate lymphoid cell homeostasis and function.

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Luke B. Roberts, Geraldine Jowett, Emily Read, Tomasz Zabinski, Rita Berkachy, Murray E. Selkirk, Ian Jackson, Umar Niazi, Nelomi Anandagoda, Masatake Araki, Kimi Araki, Jagath Kasturiarachchi, Chela James, Tariq Enver, Rachael Nimmo, Rita Antunes Dos Reis, Jane Howard, Joana F Neves, Graham M. Lord

Original languageEnglish
Pages (from-to)2725-2739
Number of pages15
JournalJournal of Immunology
Volume206
Issue number11
DOIs
Accepted/In press23 Mar 2021
Published1 Jun 2021

Bibliographical note

Funding Information: This work was supported by funding awarded by the U.K. Research and Innovation Medical Research Council to G.M.L. (Grant MR/M003493/1), the British Heart Foundation to G.M.L. (Award PG/12/36/29444) and by the U.K. National Institute for Health Research Comprehensive Biomedical Research Centre award to Guy’s and St Thomas’ National Health Service Foundation Trust, in partnership with the King’s College London and King’s College Hospital National Health Service Foundation Trust. J.F.N. acknowledges a Marie Skłodowska-Curie Fellowship, a King’s Prize fellowship, Funding Information: and a Research Councils U.K./U.K. Research and Innovation Rutherford Fund fellowship (MR/R024812/1). G.M.J. acknowledges a Ph.D. fellowship from the Wellcome Trust (203757/Z/16/A). E.R. acknowledges a Ph.D. fellowship from the Wellcome Trust (215027/Z/18/Z). N.A. was funded by a Wellcome Trust Clinical Research Training Fellowship (107387/Z/15/Z). R.N. and J.K. were funded by a Kay Kendall Leukemia Fund Intermediate Fellowship (KKL889) to R.N., and M.A. and K.A. acknowledge funding from Japan Society for the Promotion of Science KAKENHI Grant Number JP16H06276 (AdAMS). Publisher Copyright: © 2021 American Association of Immunologists. All rights reserved. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

King's Authors

Abstract

Innate lymphoid cells are central to the regulation of immunity at mucosal barrier sites, with group 2 innate lymphoid cells (ILC2s) being particularly important in type 2 immunity. In this study, we demonstrate that microRNA(miR)-142 plays a critical, cell-intrinsic role in the homeostasis and function of ILC2s. Mice deficient for miR-142 expression demonstrate an ILC2 progenitor_biased development in the bone marrow, and along with peripheral ILC2s at mucosal sites, these cells display a greatly altered phenotype based on surface marker expression. ILC2 proliferative and effector functions are severely dysfunctional following Nippostrongylus brasiliensis infection, revealing a critical role for miR-142 isoforms in ILC2-mediated immune responses. Mechanistically, Socs1 and Gfi1 expression are regulated by miR-142 isoforms in ILC2s, impacting ILC2 phenotypes as well as the proliferative and effector capacity of these cells. The identification of these novel pathways opens potential new avenues to modulate ILC2-dependent immune functions.

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