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

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.

SUBMITTER: Schmolka N 

PROVIDER: S-EPMC7233287 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature