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

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.