1. The induction and function of the anti-inflammatory fate of T H 17 cells.
- Author
-
Xu H, Agalioti T, Zhao J, Steglich B, Wahib R, Vesely MCA, Bielecki P, Bailis W, Jackson R, Perez D, Izbicki J, Licona-Limón P, Kaartinen V, Geginat J, Esplugues E, Tolosa E, Huber S, Flavell RA, and Gagliani N
- Subjects
- Animals, Cell Plasticity immunology, Disease Resistance genetics, Disease Resistance immunology, HEK293 Cells, Humans, Interleukin-10 genetics, Interleukin-10 metabolism, Interleukin-17 genetics, Interleukin-17 immunology, Interleukin-17 metabolism, Mice, Inbred C57BL, Mice, Knockout, Mice, Transgenic, Staphylococcal Infections immunology, Staphylococcal Infections microbiology, Staphylococcus aureus immunology, Staphylococcus aureus physiology, Th17 Cells metabolism, Transforming Growth Factor beta immunology, Transforming Growth Factor beta metabolism, Homeostasis immunology, Inflammation immunology, Interleukin-10 immunology, Intestines immunology, Th17 Cells immunology
- 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 TH 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 TH 17 cells. Our data thus indicate a key function of TH 17 cell plasticity in maintaining immune homeostasis, and dissect the molecular mechanisms explaining the functional flexibility of TH 17 cells with regard to environmental changes.- Published
- 2020
- Full Text
- View/download PDF