Inhibins regulate peripheral regulatory T cell induction through modulation of dendritic cell function

Abstract

We have previously reported that the absence of inhibins results in impaired dendritic cell (DC) maturation and function, leading to decreased T cell activation and diminished delayed‐type hypersensitivity responses. Here, we investigated the role of inhibins in peripheral regulatory T cell (Treg) induction in vitro and in vivo . Inhibin deficient (Inhα −/− ) mice showed an increased percentage of peripherally induced Tregs in colonic lamina propria and mesenteric lymph nodes, compared to Inhα +/+ mice, which correlated with increased expression of PD‐L1 in CD103 + and CD8α + DCs. Lipopolysaccharide‐stimulated bone marrow‐derived and ex vivo spleen‐ and lymph node‐purified CD11c + Inhα −/− DCs induced higher Tregs in vitro . Moreover, in vivo anti‐DEC205‐ovalbumin (OVA) DC targeting of mice with adoptively transferred OVA‐specific T cells showed enhanced induced peripheral Treg conversion in Inhα −/− mice. These data identify inhibins as key regulators of peripheral T cell tolerance.

A bioinformatic analysis of the inhibin-betaglycan-endoglin/CD105 network reveals prognostic value in multiple solid tumors

“…Wnt has been shown to regulate INHA transcription in rat adrenal cortex and could increase INHA expression in certain tumors to promote tumorigenesis [ 163 ]. Recent evidence indicates increased PD-L1 in dendritic cells in INHA -/- mice [ 164 ]. We speculate that increased INHA in tumors may inhibit PD-L1 expression perhaps via antagonistic effect on other TGF-β members, increasing anti-tumor immune responses.…”