MicroRNA-142 regulates gut associated lymphoid tissues and group 3 innate lymphoid cells.

Autor:	Roberts LB; Lydia Becker Institute of Immunology and Inflammation, University of Manchester, M13 9PL, United Kingdom. Electronic address: luke.roberts@manchester.ac.uk., Neves JF; Centre for Host-Microbiome Interactions, King's College London, Great Maze Pond, London SE1 9RT, United Kingdom., Lee DCH; Lydia Becker Institute of Immunology and Inflammation, University of Manchester, M13 9PL, United Kingdom., Valpione S; The Christie NHS Foundation Trust, 550 Wilmslow Road, M20 4BX Manchester, United Kingdom; Division of Cancer Sciences, The University of Manchester, Oxford Road, M13 9PL Manchester, United Kingdom; Cancer Research UK National Biomarker Centre, Wilmslow Road, M20 4BX Manchester, United Kingdom., Tachó-Piñot R; Lydia Becker Institute of Immunology and Inflammation, University of Manchester, M13 9PL, United Kingdom., Howard JK; School of Cardiovascular and Metabolic Medicine & Sciences, King's College London, Great Maze Pond, London SE1 9RT, United Kingdom., Hepworth MR; Lydia Becker Institute of Immunology and Inflammation, University of Manchester, M13 9PL, United Kingdom., Lord GM; Lydia Becker Institute of Immunology and Inflammation, University of Manchester, M13 9PL, United Kingdom; Centre for Gene Therapy and Regenerative Medicine, School of Basic and Medical Biosciences, Faculty of Life Sciences and Medicine, King's College London, United Kingdom. Electronic address: graham.lord@kcl.ac.uk.
Jazyk:	angličtina
Zdroj:	Mucosal immunology [Mucosal Immunol] 2024 Sep 07. Date of Electronic Publication: 2024 Sep 07.
DOI:	10.1016/j.mucimm.2024.09.001
Abstrakt:	The transcriptomic signatures that shape responses of innate lymphoid cells (ILCs) have been well characterised, however post-transcriptional mechanisms which regulate their development and activity remain poorly understood. We demonstrate that ILC groups of the intestinal lamina propria express mature forms of microRNA-142 (miR-142), an evolutionarily conserved microRNA family with several non-redundant regulatory roles within the immune system. Germline Mir142 deletion alters intestinal ILC compositions, resulting in the absence of T-bet + populations and significant defects in the cellularity and phenotypes of ILC3 subsets including CCR6 + LTi-like ILC3s. These effects were associated with decreased pathology in an innate-immune cell driven model of colitis. Furthermore, Mir142 -/- mice demonstrate defective development of gut-associated lymphoid tissues, including a complete absence of mature Peyer's patches. Conditional deletion of Mir142 in ILC3s (Rorc Δ Mir142 ) supported cell-intrinsic roles for these microRNAs in establishing or maintaining cellularity and functions of LTi-like ILC3s in intestinal associated tissues. RNAseq analysis revealed several target genes and biological pathways potentially regulated by miR-142 microRNAs in these cells. Finally, lack of Mir142 in ILC3 led to elevated IL-17A production. These data broaden our understanding of immune system roles of miR-142 microRNAs, identifying these molecules as critical post-transcriptional regulators of ILC3s and intestinal mucosal immunity. Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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