MicroRNA-146a controls functional plasticity in T cells by targeting NOD1

Nina Schmolka, Pedro H. Papotto, Paula Vargas Romero, Tiago Amado, Francisco J. Enguita, Ana Amorim, Ana F. Rodrigues, Katrina E. Gordon, Ana S. Coroadinha, Mark Boldin, Karine Serre, Amy H. Buck, Anita Q. Gomes, Bruno Silva-Santos

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7 Citations (Scopus)

Abstract

T cells are major providers of proinflammatory cytokines. They are preprogrammed in the mouse thymus into distinct subsets producing either interleukin-17 (IL-17) or interferon- (IFN-), which segregate with CD27 expression. In the periphery, CD27 (27 ) T cells can be induced under inflammatory conditions to coexpress IL-17 and IFN-; the molecular basis of this functional plasticity remains to be determined. On the basis of differential microRNA (miRNA) expression analysis and modulation in T cell subsets, we identified miR-146a as a thymically imprinted post-transcriptional brake to limit IFN- expression in 27 T cells in vitro and in vivo. On the basis of biochemical purification of Argonaute 2–bound miR-146a targets, we identified Nod1 to be a relevant mRNA target that regulates T cell plasticity. In line with this, Nod1-deficient mice lacked multifunctional IL-17 + IFN- + 27 cells and were more susceptible to Listeria monocytogenes infection. Our studies establish the miR-146a/NOD1 axis as a key determinant of T cell effector functions and plasticity.

Original languageEnglish
Article numbereaao1392
JournalScience Immunology
Volume3
Issue number23
DOIs
Publication statusPublished - 1 Jan 2018

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    Schmolka, N., Papotto, P. H., Romero, P. V., Amado, T., Enguita, F. J., Amorim, A., ... Silva-Santos, B. (2018). MicroRNA-146a controls functional plasticity in T cells by targeting NOD1. Science Immunology, 3(23), [eaao1392]. https://doi.org/10.1126/sciimmunol.aao1392