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Sci Immunol. 2018 May 4;3(23). pii: eaao1392. doi: 10.1126/sciimmunol.aao1392.

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

Author information

1
Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisboa, Portugal. nina.schmolka@uzh.ch anitagomes@medicina.ulisboa.pt bssantos@medicina.ulisboa.pt.
2
Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisboa, Portugal.
3
iBET, Instituto de Biologia Experimental e Tecnológica, 2780-157 Oeiras, Portugal.
4
Instituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa, 2780-157 Oeiras, Portugal.
5
Institute of Immunology and Infection and Centre for Immunity, Infection and Evolution, University of Edinburgh, Edinburgh EH9 3FL, UK.
6
Department of Molecular and Cellular Biology, Beckman Research Institute, City of Hope, Duarte, CA 91010, USA.
7
Escola Superior de Tecnologia da Saúde de Lisboa, 1990-096 Lisboa, Portugal.

Abstract

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 monocytogenes infection. Our studies establish the miR-146a/NOD1 axis as a key determinant of γδ T cell effector functions and plasticity.

PMID:
29728425
DOI:
10.1126/sciimmunol.aao1392

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