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

## TL;DR

Inhibins help activate T cells, aid their migration, and influence their differentiation into Th1 or Th17 cells, playing a key role in immune responses.

## Contribution

Inhibins produced by T cells regulate activation, migration, and Th1/Th17 differentiation through autocrine signaling.

## Key findings

- Inhα−/− T cells show reduced activation markers and impaired migration toward CCL19/CCL21.
- Inhα−/− T cells differentiate less into Th1 and more into Th17 cells.
- Recombinant Inh A restores Th1/Th17 balance without affecting Th1 differentiation.

## Abstract

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.

Activins/inhibins modulate immune responses. Here, we show that inhibins can be produced very early after T cell activation and can act in an autocrine way, favoring Th1 versus Th17 differentiation and CCL19/CCL21 mediated migration. Recombinant inhibin A can restore the Th1/Th17 balance, highlighting the role of inhibins as key regulators of T cell function and immune homeostasis.