TH17 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 TH17 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 TH17 cells. Our data thus indicate a key function of TH17 cell plasticity in maintaining immune homeostasis, and dissect the molecular mechanisms explaining the functional flexibility of TH17 cells with regard to environmental changes.

The induction and function of the anti-inflammatory fate of TH17 cells / H. Xu, T. Agalioti, J. Zhao, B. Steglich, R. Wahib, M.C.A. Vesely, P. Bielecki, W. Bailis, R. Jackson, D. Perez, J. Izbicki, P. Licona-Limon, V. Kaartinen, J. Geginat, E. Esplugues, E. Tolosa, S. Huber, R.A. Flavell, N. Gagliani. - In: NATURE COMMUNICATIONS. - ISSN 2041-1723. - 11:1(2020 Jul 03).

The induction and function of the anti-inflammatory fate of TH17 cells

J. Geginat;
2020

Abstract

TH17 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 TH17 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 TH17 cells. Our data thus indicate a key function of TH17 cell plasticity in maintaining immune homeostasis, and dissect the molecular mechanisms explaining the functional flexibility of TH17 cells with regard to environmental changes.
Animals; Cell Plasticity; Disease Resistance; HEK293 Cells; Homeostasis; Humans; Inflammation; Interleukin-10; Interleukin-17; Intestines; Mice, Inbred C57BL; Mice, Knockout; Mice, Transgenic; Staphylococcal Infections; Staphylococcus aureus; Th17 Cells; Transforming Growth Factor beta
Settore MED/04 - Patologia Generale
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/848506
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