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MicroRNA-142 regulates gut associated lymphoid tissues and group 3 innate lymphoid cells
Roberts, L. B. Neves, J. F. Lee, D. C. H. Valpione, S. Tachó-Piñot, R. Howard, J. K. Hepworth, M. R. Lord, G. M.
Roberts, L. B.
Neves, J. F.
Lee, D. C. H.
Valpione, S.
Tachó-Piñot, R.
Howard, J. K.
Hepworth, M. R.
Lord, G. M.
Abstract
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 Delta Mir142) supported cell-intrinsic roles for these microRNAs in establishing or maintaining cellularity and functions of LTilike 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.
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Date
2025
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Collections
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Article
Citation
Roberts LB, Neves JF, Lee DCH, Valpione S, Tachó-Piñot R, Howard JK, et al. MicroRNA-142 regulates gut associated lymphoid tissues and group 3 innate lymphoid cells. Mucosal immunology. 2025 FEB;18(1):39-52. PubMed PMID: WOS:001429257300001. English.