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A key role for microRNAs in regulating IL-17 versus IFN-γ production by γδ T cells
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Advisor(s)
Abstract(s)
γδ T cells are key providers of proinflammatory cytokines in various contexts of (patho)physiology. They are preprogrammed in the 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 T cells, which usually express IL-17, can be induced to coexpress IL-17 and IFN-γ. We have previously found that miR-146a was selectively enriched in these cells and restricted their IFN-γ production by targeting Nod1 mRNA. We aim at further dissecting microRNA-mediated regulation of effector γδ T cell differentiation independently of the use of surface markers, which do not allow the isolation of pure populations of IL-17+ or IFN-γ+ γδ T cells. Thus, we isolated these pure γδ T cell populations from peripheral lymphoid organs of a double reporter IL-17-GFP: IFN-γ-YFP mouse strain and subjected them to next-generation sequencing analysis of both microRNA and mRNA repertoires, which allowed us to identify miRNA and mRNA signatures directly associated with cytokine expression. Furthermore, differentially expressed miRNAs and mRNAs were bioinformatically integrated into networks that allowed the prediction of 6 and 3 miRNAs targeting key determinants of the IL-17 and IFN-γ programs of γδ T cells, respectively. Preliminary results, based on gain-of-function studies on fetal liver progenitor cells co-cultured with OP9-DL1 cells indicate that miR-326 and miR-450b may regulate γδ T cell development, inhibiting IFN-γ production. Further molecular assays are being performed on peripheral γδ T cells to provide a broader 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 IL-17 production IFN-γ production γδ T cells
Citation
Inácio D, Amado T, Sobral D, Enguita F, Gomes AQ, Silva-Santos B. A key role for microRNAs in regulating IL-17 versus IFN-γ production by γδ T cells. In: RNA Regulatory Networks, 3rd International Symposium on Frontiers in Molecular Science, Pavilhão do Conhecimento, Lisbon (Portugal), June 26-28, 2019.