Pathogen-induced human T H17 cells produce IFN-γ or IL-10 and are regulated by IL-1β

Christina E. Zielinski, Federico Mele, Dominik Aschenbrenner, David Jarrossay, Francesca Ronchi, Marco Gattorno, Silvia Monticelli, Antonio Lanzavecchia, Federica Sallusto

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Abstract

IL-17-producing CD4 + T helper cells (T H17) have been extensively investigated in mouse models of autoimmunity 1. However, the requirements for differentiation and the properties of pathogen-induced human T H17 cells remain poorly defined. Using an approach that combines the in vitro priming of naive T cells with the ex vivo analysis of memory T cells, we describe here two types of human T H17 cells with distinct effector function and differentiation requirements. Candida albicans-specific T H17 cells produced IL-17 and IFN-γ, but no IL-10, whereas Staphylococcus aureus-specific T H17 cells produced IL-17 and could produce IL-10 upon restimulation. IL-6, IL-23 and IL-1β contributed to T H17 differentiation induced by both pathogens, but IL-1β was essential in C. albicans-induced T H17 differentiation to counteract the inhibitory activity of IL-12 and to prime IL-17/IFN-γ double-producing cells. In addition, IL-1β inhibited IL-10 production in differentiating and in memory T H17 cells, whereas blockade of IL-1β in vivo led to increased IL-10 production by memory T H17 cells. We also show that, after restimulation, T H17 cells transiently downregulated IL-17 production through a mechanism that involved IL-2-induced activation of STAT5 and decreased expression of ROR-γt. Taken together these findings demonstrate that by eliciting different cytokines C. albicans and S. aureus prime T H17 cells that produce either IFN-γ or IL-10, and identify IL-1β and IL-2 as pro-and anti-inflammatory regulators of T H17 cells both at priming and in the effector phase.

Original languageEnglish
Pages (from-to)514-518
Number of pages5
JournalNature
Volume484
Issue number7395
DOIs
Publication statusPublished - Apr 26 2012

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Interleukin-1
Interleukin-10
Interleukin-17
Candida albicans
Helper-Inducer T-Lymphocytes
Interleukin-2
Staphylococcus aureus
Interleukin-23
T-Lymphocytes
Interleukin-12
Autoimmunity
Interleukin-6
Anti-Inflammatory Agents
Down-Regulation
Cytokines

ASJC Scopus subject areas

  • General

Cite this

Zielinski, C. E., Mele, F., Aschenbrenner, D., Jarrossay, D., Ronchi, F., Gattorno, M., ... Sallusto, F. (2012). Pathogen-induced human T H17 cells produce IFN-γ or IL-10 and are regulated by IL-1β. Nature, 484(7395), 514-518. https://doi.org/10.1038/nature10957

Pathogen-induced human T H17 cells produce IFN-γ or IL-10 and are regulated by IL-1β. / Zielinski, Christina E.; Mele, Federico; Aschenbrenner, Dominik; Jarrossay, David; Ronchi, Francesca; Gattorno, Marco; Monticelli, Silvia; Lanzavecchia, Antonio; Sallusto, Federica.

In: Nature, Vol. 484, No. 7395, 26.04.2012, p. 514-518.

Research output: Contribution to journalArticle

Zielinski, CE, Mele, F, Aschenbrenner, D, Jarrossay, D, Ronchi, F, Gattorno, M, Monticelli, S, Lanzavecchia, A & Sallusto, F 2012, 'Pathogen-induced human T H17 cells produce IFN-γ or IL-10 and are regulated by IL-1β', Nature, vol. 484, no. 7395, pp. 514-518. https://doi.org/10.1038/nature10957
Zielinski CE, Mele F, Aschenbrenner D, Jarrossay D, Ronchi F, Gattorno M et al. Pathogen-induced human T H17 cells produce IFN-γ or IL-10 and are regulated by IL-1β. Nature. 2012 Apr 26;484(7395):514-518. https://doi.org/10.1038/nature10957
Zielinski, Christina E. ; Mele, Federico ; Aschenbrenner, Dominik ; Jarrossay, David ; Ronchi, Francesca ; Gattorno, Marco ; Monticelli, Silvia ; Lanzavecchia, Antonio ; Sallusto, Federica. / Pathogen-induced human T H17 cells produce IFN-γ or IL-10 and are regulated by IL-1β. In: Nature. 2012 ; Vol. 484, No. 7395. pp. 514-518.
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