Research ArticleT CELLS

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

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Science Immunology  04 May 2018:
Vol. 3, Issue 23, eaao1392
DOI: 10.1126/sciimmunol.aao1392

Micromanaging NOD1 in T cells

MicroRNAs (miRNAs) represent an additional layer of regulation between gene transcription and translation of mRNA. Schmolka et al. document miR-146a as being highly expressed in a subset of γδ T cells, CD27 γδ T cells that can coexpress cytokines interleukin-17 and interferon-γ (IFN-γ). They report that miR-146a represses expression of IFN-γ in CD27 γδ T cells by targeting nucleotide-binding oligomerization domain-containing protein 1 (NOD1), a pattern recognition receptor (PRR) that recognizes bacterial peptidoglycan. Deletion of NOD1 impaired production of IFN-γ in CD27 γδ T cells, albeit precisely how NOD1 regulates IFN-γ remains to be seen. The study adds to the increasing appreciation of the noncanonical functions of PRRs.


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.

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