Cited by 922Psoriasis: Treatment and PathogenesisT-cell and B-cell ImmunologyIL-33, ST2, and ILC Pathways

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Pathogen-induced human TH17 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·2012·Nature

DOI 10.1038/nature10957

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Abstract

IL-17-producing CD4+ T helper cells (TH17) have been extensively investigated in mouse models of autoimmunity. However, the requirements for differentiation and the properties of pathogen-induced human TH17 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 TH17 cells with distinct effector function and differentiation requirements. Candida albicans-specific TH17 cells produced IL-17 and IFN-γ, but no IL-10, whereas Staphylococcus aureus-specific TH17 cells produced IL-17 and could produce IL-10 upon restimulation. IL-6, IL-23 and IL-1β contributed to TH17 differentiation induced by both pathogens, but IL-1β was essential in C. albicans-induced TH17 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 TH17 cells, whereas blockade of IL-1β in vivo led to increased IL-10 production by memory TH17 cells. We also show that, after restimulation, TH17 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 TH17 cells that produce either IFN-γ or IL-10, and identify IL-1β and IL-2 as pro- and anti-inflammatory regula…

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Self-citation
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Authors: Zielinski, C. E., Mele, F., Aschenbrenner, D., Jarrossay, D., Ronchi, F., Gattorno, M., Monticelli, S., Lanzavecchia, A., & Sallusto, F.
Affiliations: Institute for Research in Biomedicine (CH)
Istituto Giannina Gaslini (IT)
ETH Zurich (CH)
Corresponding author: Zielinski, Christina E.
Sallusto, Federica
ORCID: Zielinski, Christina E.
Mele, Federico
Aschenbrenner, Dominik
Jarrossay, David
Ronchi, Francesca
Gattorno, Marco
Monticelli, Silvia
Lanzavecchia, Antonio
Sallusto, Federica
Venue: Nature
Publisher: Springer Science and Business Media LLC
Published: 2012-04
Volume: 484
Issue: 7395
Pages: 514-518
ISSN: 0028-0836 (ISSN-L)
1476-4687
DOI: 10.1038/nature10957
OpenAlex: W2144288685
Cited by: 919
References: 31
Citations by year: 2026: 25 · 2025: 39 · 2024: 62 · 2023: 49 · 2022: 55 · 2021: 70 · 2020: 63 · 2019: 71 · 2018: 68 · 2017: 78 · 2016: 72 · 2015: 72 · 2014: 74 · 2013: 82 · 2012: 38
FWCI: 37.06
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
www.springer.com/tdm (vor)
Locations: Nature (publishedVersion)
PubMed (publishedVersion)
RePEc: Research Papers in Economics (submittedVersion)
Topics: Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
Life Sciences › Immunology and Microbiology › Immunology › IL-33, ST2, and ILC Pathways
Keywords: Th17 cells, Candida albicans, Staphylococcus aureus, IL-1β, IL-17, interferon-gamma, IL-10, interleukin-2, STAT5, RORγt, IL-12, IL-23, interleukin-6, T cell differentiation, memory T cells, fungal infection, bacterial infection
MeSH terms: Candida albicans, Cell Differentiation, Humans, Immunologic Memory, Interferon-gamma, Interleukin-2, Lymphocyte Activation, Staphylococcus aureus, Tumor Necrosis Factor-alpha, Down-Regulation, Interleukin-10, Antigen Presentation, Interleukin-17, STAT5 Transcription Factor, Interleukin-1beta, Nuclear Receptor Subfamily 1, Group F, Member 3, Th17 Cells

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Pathogen-induced human TH17 cells produce IFN-γ or IL-10 and are regulated by IL-1β

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