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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, Sara Tachó-Piñot, R. Howard, J. K. Hepworth, M. R. Lord, G. M.
Roberts, L. B.
Neves, J. F.
Lee, D. C. H.
Valpione, Sara
Tachó-Piñot, R.
Howard, J. K.
Hepworth, M. R.
Lord, G. M.
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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(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.
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Date
2024
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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. 2024 Sep 7. PubMed PMID: 39245145. Epub 2024/09/09. eng.