| First Author | Schmolka N | Year | 2018 |
| Journal | Sci Immunol | Volume | 3 |
| Issue | 23 | PubMed ID | 29728425 |
| Mgi Jnum | J:314308 | Mgi Id | MGI:6791688 |
| Doi | 10.1126/sciimmunol.aao1392 | Citation | Schmolka N, et al. (2018) MicroRNA-146a controls functional plasticity in gammadelta T cells by targeting NOD1. Sci Immunol 3(23) |
| abstractText | gammadelta 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(-) gammadelta (gammadelta27(-)) 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 gammadelta T cell subsets, we identified miR-146a as a thymically imprinted post-transcriptional brake to limit IFN-gamma expression in gammadelta27(-) 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 gammadelta T cell plasticity. In line with this, Nod1-deficient mice lacked multifunctional IL-17(+) IFN-gamma(+) gammadelta27(-) cells and were more susceptible to Listeria monocytogenes infection. Our studies establish the miR-146a/NOD1 axis as a key determinant of gammadelta T cell effector functions and plasticity. |
