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Publication
A key role for microRNAs in regulating IL-17 versus IFN-g production by gamma-delta T cells
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Advisor(s)
Abstract(s)
γδ T cells are an important source of the pro-inflammatory cytokines IL-17 and IFN-γ under (patho)physiologic conditions. In the mouse, CD27+ γδ T cells are committed to IFN-γ expression, whereas their CD27- counterparts make IL-17 but are capable of co-expressing both cytokines under inflammatory conditions. We aim to characterize a novel layer of microRNA-mediated regulation of effector γδ T cell differentiation. First, by comparing the microRNA pools of the two CD27-based γδ T cell subsets, we found that miR-146a was selectively enriched in CD27- γδ T cells and restricted their IFN-γ production by targeting Nod1 mRNA. Next, to overcome the caveat of using surface markers, which do not allow isolation of pure populations of IL-17 or IFN-γ producing γδ T cells, we used a double reporter IL-17-GFP: IFNg-YFP mouse strain. Pure IL-17+ or IFN-γ+ γδ T cell populations were isolated from peripheral lymphoid organs and subjected to next-generation sequencing analysis of both microRNA and mRNA repertoires. This allowed us to identify, for the first time, miRNA and mRNA signatures directly associated with cytokine expression, rather than TCR Vγ usage of maturation markers. Furthermore, differentially expressed miRNAs and mRNAs were bioinformatically integrated into networks that allowed the identification of 6 miRNAs predicted to target key determinants of the IL-17 program; and 3 miRNA candidates for the IFN-γ program of γδ T cells. Ongoing molecular assays provide an unprecedented functional characterization of the impact of microRNAs on the identity and differentiation of effector γδ T cell subsets.
Description
Keywords
Immune system MicroRNA Proinflammatory cytokines T cell differentiation
Citation
Amado T, Schmolka N, Sobral D, Enguita F, Inácio D, Gomes AQ, et al. A key role for microRNAs in regulating IL-17 versus IFN-g production by gamma-delta T cells. In: 5th European Congress of Immunology, Amsterdam (Netherlands), September 2-5, 2018. p. 193.