MicroRNA-146a controls functional plasticity in γδ T cells by targeting NOD1
γδ 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 monocytogenesinfection. Our studies establish the miR-146a/NOD1 axis as a key determinant of γδ T cell effector functions and plasticity.
Authors: Schmolka N1, Papotto PH2, Romero PV2, Amado T2, Enguita FJ2, Amorim A2, Rodrigues AF3,4, Gordon KE5, Coroadinha AS3,4, Boldin M6, Serre K2, Buck AH5, Gomes AQ1,7, Silva-Santos B1
Citation: Sci Immunol 3, (2018).