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

Nina Schmolka, Pedro H Papotto, Paula Vargas Romero, Tiago Amado, Francisco J Enguita, Ana Amorim, Ana F Rodrigues, Katrina E Gordon, Ana S Coroadinha, Mark Boldin, Karine Serre, Amy H Buck, Anita Q Gomes, Bruno Silva-Santos

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

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.

Original languageEnglish
Number of pages13
JournalScience Immunology
Issue number23
Publication statusPublished - 4 May 2018

Keywords / Materials (for Non-textual outputs)

  • Animals
  • DNA-Binding Proteins/genetics
  • Listeria monocytogenes
  • Listeriosis/immunology
  • Mice, Inbred C57BL
  • Mice, Knockout
  • MicroRNAs/genetics
  • Nod1 Signaling Adaptor Protein/genetics
  • T-Lymphocyte Subsets/immunology


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