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Xu, Hao; Agalioti, Theodora; Zhao, Jun; Steglich, Babett; Wahib, Ramez; Vesely, Maria Carolina Amezcua; Bielecki, Piotr; Bailis, Will; Jackson, Ruaidhri; Perez, Daniel; Izbicki, Jakob; Licona-Limon, Paula; Kaartinen, Vesa; Geginat, Jens; Esplugues, Enric; Tolosa, Eva; Huber, Samuel; Flavell, Richard A; Gagliani, Nicola (2020)

THE INDUCTION AND FUNCTION OF THE ANTI-INFLAMMATORY FATE OF T(H)17 CELLS

Nat Commun 11(1):
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T17 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 T17 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 T17 cells. Our data thus indicate a key function of T17 cell plasticity in maintaining immune homeostasis, and dissect the molecular mechanisms explaining the functional flexibility of T17 cells with regard to environmental changes.