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Soldevila, Gloria; Ortega-Francisco, Sandra A; Morales, Alexandra; de Oca, Selina Montes; Albarran, Adrian; Hernandez-Campos, Oscar; Olguin-Alor, Roxana
The Journal of immunology (1950), 05/2020, Volume: 204, Issue: 1_SupplementJournal Article
Abstract Inhibins, ligands of the TGFβ superfamily, and their molecular pair, TGF-β type III receptor (TβRIII), have been shown to regulate the development of T cells within the thymus. Moreover, we recently reported that TβRIII acts as an activation marker after TCR stimulation However, the intrinsic role of Inhibins in T cell activation and differentiation is currently unknown. Here, we describe for the first time that T cells are able to produce Inhibin A after a polyclonal TCR stimulation which raises the possibility of this ligand playing a direct role in T cell responses. Interestingly, Inhα−/− naïve T cells showed lower expression of activation markers, including TβRIII, after TCR stimulation, compared with their wild type counterparts. Moreover, Inhα−/− naïve T cells showed a significant decrease in Th1 differentiation under polarizing conditions in vitro, that correlated with lower levels of activation. Furthermore, when we evaluated the differentiation of Inhα−/− naïve T cells towards Th17, a TGFβ-dependent lineage, we observed an increase in the percentage of IL-17+ T cells compared to wild type. Interestingly, this altered Th differentiation could be rescued by addition of exogenous Inhihin A, leading to a significant decrease in IL-17 production and a trend towards an increase in IFNγ production. These data suggest that Inhibins play an intrinsic role during T cell activation and may be key modulators of T effector cell differentiation during an immune response.
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