Pathogen-induced human TH17 cells produce IFN-γ or IL-10 and are regulated by IL-1β
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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Th17 cells in different tissue sites can show distinct transcriptional profiles associated with homeostatic or pathogenic functions.
“analysis of Th17 cells in different tissue sites has revealed that Th17 cells may exhibit distinct transcriptional profiles associated with either homeostatic or pathogenic functions”
From TH17 cell heterogeneity and its role in tissue inflammation (2023) · cites this paper as [39]
In vitro polarization with IL-6 and TGF-β generates non-pathogenic Th17 cells that produce IL-17 but induce little or no tissue inflammation or autoimmunity.
“In vitro polarization of naïve CD4+ T helper cells with IL-6 and TGF-ß generates Th17 cells that produce IL-17 but induce little or no tissue inflammation or autoimmunity (non-pathogenic Th17 cells)”
From TH17 cell heterogeneity and its role in tissue inflammation (2023) · cites this paper as [39]
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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
- Venue
- Nature
- Published
- 2012-04
- Volume
- 484
- Issue
- 7395
- Pages
- 514-518
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- 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
- 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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