Browsing by Author "Rodrigues, Ana F."
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- MicroRNA-146a controls functional plasticity in γδ T cells by targeting NOD1Publication . Schmolka, Nina; Papotto, Pedro H.; Romero, Paula Vargas; Amado, Tiago; Enguita, Francisco J.; Amorim, Ana; Rodrigues, Ana F.; Gordon, Katrina E.; Coroadinha, Ana S.; Boldin, Mark; Serre, Karine; Buck, Amy H.; Gomes, Anita Quintal; Silva-Santos, Brunoγδ 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.