Details

Autor(en) / Beteiligte

• Fuente‐Granada, Marisol
• Olguín‐Alor, Roxana
• Ortega‐Francisco, Sandra
• Bonifaz, Laura C.
• Soldevila, Gloria

Titel

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

Ist Teil von

• FEBS open bio, 2019-01, Vol.9 (1), p.137-147

Ort / Verlag

England: John Wiley & Sons, Inc

Erscheinungsjahr

2019

Link zum Volltext

Quelle

Wiley Online Library - AutoHoldings Journals

Beschreibungen/Notizen

• 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. Dendritic cells (DCs) play a key role in the induction of peripherally induced regulatory T cells (Tregs) under homeostatic and inflammatory conditions. This study demonstrates that inhibins modulate the induction of Tregs from naïve T cells in the periphery through promoting DC maturation and function. Inhibin‐deficient DCs showed increased levels of PD‐L1, correlating with increased induction of Tregs in vitro and in vivo.