The induction and function of the anti-inflammatory fate of TH17 cells
Hao Xu, Theodora Agalioti, Jun Zhao, Babett Steglich, Ramez Wahib, María Carolina Amezcua Vesely, Piotr Bielecki, Will Bailis, Ruaidhrí Jackson, Daniel Pérez, Jakob R. Izbicki, Paula Licona-Limón, Vesa Kaartinen, Jens Geginat, Enric Esplugues, Eva Tolosa, Samuel Huber, Richard A. Flavell, Nicola Gagliani
Abstract
Abstract T H 17 cells exemplify environmental immune adaptation: they can acquire both a pathogenic and an anti-inflammatory fate. However, it is not known whether the anti-inflammatory fate is merely a vestigial trait, or whether it serves to preserve the integrity of the host tissues. Here we show that the capacity of T H 17 cells to acquire an anti-inflammatory fate is necessary to sustain immunological tolerance, yet it impairs immune protection against S . aureus . Additionally, we find that TGF-β signalling via Smad3/Smad4 is sufficient for the expression of the anti-inflammatory cytokine, IL-10, in T H 17 cells. Our data thus indicate a key function of T H 17 cell plasticity in maintaining immune homeostasis, and dissect the molecular mechanisms explaining the functional flexibility of T H 17 cells with regard to environmental changes.