Inhibins/TGFβRIII modulate T cell activation and Th1/Th17 effector differentiation

• Published in: The Journal of immunology (1950) 2020-05, Vol.204 (1_Supplement), p.78-78.23
• Main Authors: Soldevila, Gloria, Ortega-Francisco, Sandra A, Morales, Alexandra, de Oca, Selina Montes, Albarran, Adrian, Hernandez-Campos, Oscar, Olguin-Alor, Roxana
• Format: Article
• Language: English
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.204.Supp.78.23

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.