Key role for inhibins in effective T cell activation, migration and Th17 differentiation.

Our group has previously reported that inhibin and its molecular pair, TGF-β type III receptor (TβRIII), regulate T cell development within the thymus. In addition, inhibins play a key role in immune tolerance through the modulation of dendritic cell (DC) maturation and peripheral Treg induction. However, the functional role of inhibins in T cell activation and differentiation is currently unknown. Here, we demonstrate that inhibins are produced by activated T cells and play a role during T cell activation, migration, and functional Th differentiation. Specifically, stimulation of Inhα^-/- naïve T cells resulted in decreased expression of early activation markers, including CD69, CD25, and TβRIII, compared to Inhα^+/+ T cells. Additionally, we analyzed the migratory potential of Inhα^-/- T cells toward CCR7 ligands and showed an impaired in vitro chemotaxis toward CCL21 and CCL19, which correlated with a decreased homing to peripheral lymph nodes using in vivo competitive assays. To evaluate the impact of inhibins on Th differentiation, we performed in vitro polarization cultures under skewing conditions. Interestingly, Inhα^-/- naïve T cells showed a decreased differentiation to Th1 cells, while the induction of Th17 cells was significantly increased when compared with Inhα^+/+. This preferential polarization of Inhα^-/- toward Th17 was reversed by the addition of recombinant Inh A, without altering the differentiation of Inhα^-/- Th1. Our data demonstrate that inhibins regulate T cell effector differentiation and homing and thus, may be considered new players in T cell immune responses.