Schmolka, NinaPapotto, Pedro H.Romero, Paula VargasAmado, TiagoEnguita, Francisco J.Amorim, AnaRodrigues, Ana F.Gordon, Katrina E.Coroadinha, Ana S.Boldin, MarkSerre, KarineBuck, Amy H.Gomes, Anita QuintalSilva-Santos, Bruno2018-06-112018-06-112018-05Schmolka N, Papotto PH, Romero PV, Amado T, Enguita FJ, Gomes AQ, et al. MicroRNA-146a controls functional plasticity in γδ T cells by targeting NOD1. Sci Immunol. 2018;3(23).http://hdl.handle.net/10400.21/8618γδ 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-γ (IFN-γ), which segregate with CD27 expression. In the periphery, CD27- γδ (γδ27-) T cells can be induced under inflammatory conditions to coexpress IL-17 and IFN-γ; the molecular basis of this functional plasticity remains to be determined. On the basis of differential microRNA (miRNA) expression analysis and modulation in γδ T cell subsets, we identified miR-146a as a thymically imprinted post-transcriptional brake to limit IFN-γ expression in γδ27- 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 γδ T cell plasticity. In line with this, Nod1-deficient mice lacked multifunctional IL-17+ IFN-γ+ γδ27- cells and were more susceptible to Listeria monocytogenes infection. Our studies establish the miR-146a/NOD1 axis as a key determinant of γδ T cell effector functions and plasticity.engT cellsProinflammatory cytokinesPTDC/BEX-BCM/3592/2014journal article10.1126/sciimmunol.aao1392