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

作者：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 Q^*; Silva Santos Bruno^*

来源：Science Immunology, 2018, 3(23): UNSP eaao1392.

DOI：10.1126/sciimmunol.aao1392

gamma delta 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-gamma (IFN-gamma), which segregate with CD27 expression. In the periphery, CD27(-) gamma delta (gamma delta 27(-)) T cells can be induced under inflammatory conditions to coexpress IL-17 and IFN-gamma; the molecular basis of this functional plasticity remains to be determined. On the basis of differential microRNA (miRNA) expression analysis and modulation in gamma delta T cell subsets, we identified miR-146a as a thymically imprinted post-transcriptional brake to limit IFN-gamma expression in gamma delta 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 gamma delta T cell plasticity. In line with this, Nod1-deficient mice lacked multifunctional IL-17(+)IFN-gamma(+) gamma delta 27(-) cells and were more susceptible to Listeria monocytogenes infection. Our studies establish the miR-146a/NOD1 axis as a key determinant of gamma delta T cell effector functions and plasticity.

• 出版日期2018-5
• 单位河北医科大学