biostudies-literatureRoberts LBThe Royal SocietyResearch Councils UKWellcome TrustUK Research and InnovationBiotechnology and Biological Sciences Research Council39-52https://www.ebi.ac.uk/biostudies/studies/S-EPMC11835792biostudies-literatureUnknown18(1)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. FurthermMucosal immunologyMicroRNA-142 regulates gut associated lymphoid tissues and group 3 innate lymphoid cells.PMC11835792105644/Z/14/ZBB/T014482/1Valpione SLee DCHLord GMTacho-Pinot RHepworth MRRoberts LBNeves JFHoward JKfalseMicroRNA-142 regulates gut associated lymphoid tissues and group 3 innate lymphoid cells.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. Furtherm2025-01-01T00:00:00Z2025 Feb2025-04-04T00:31:31.901Z2025-04-04T00:31:31.901ZS-EPMC118357923924514510.1016/j.mucimm.2024.09.001