TGFβ in the Context of an Inflammatory Cytokine Milieu Supports De Novo Differentiation of IL-17-Producing T Cells

Veldhoen, Marc; Hocking, Richard J.; Atkins, Christopher J.; Locksley, Richard M.; Stockinger, Brigitta

doi:10.1016/j.immuni.2006.01.001

Cited by 3,605T-cell and B-cell ImmunologyPsoriasis: Treatment and PathogenesisTGF-β signaling in diseases

TGFβ in the Context of an Inflammatory Cytokine Milieu Supports De Novo Differentiation of IL-17-Producing T Cells

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Veldhoen, Marc, Hocking, Richard J., Atkins, Christopher J., Locksley, Richard M., Stockinger, Brigitta·2006·Immunity

DOI 10.1016/j.immuni.2006.01.001

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Abstract

We describe de novo generation of IL-17-producing T cells from naive CD4 T cells, induced in cocultures of naive CD4 T cells and naturally occurring CD4+ CD25+ T cells (Treg) in the presence of TLR3, TLR4, or TLR9 stimuli. Treg can be substituted by TGFbeta1, which, together with the proinflammatory cytokine IL-6, supports the differentiation of IL-17-producing T cells, a process that is amplified by IL-1beta and TNFalpha. We could not detect a role for IL-23 in the differentiation of IL-17-producing T cells but confirmed its importance for their survival and expansion. Transcription factors GATA-3 and T-bet, as well as its target Hlx, are absent in IL-17-producing T cells, and they do not express the negative regulator for TGFbeta signaling, Smad7. Our data indicate that, in the presence of IL-6, TGFbeta1 subverts Th1 and Th2 differentiation for the generation of IL-17-producing T cells.

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There is an absolute requirement for persistent IL-6 signaling to maintain the Th17 genetic program, and thus Th17 cells.
“Here, we report that in addition to its key role in Th17 cell induction (3, 4), there is an absolute requirement for persistent IL-6 signaling to maintain the Th17 genetic program, and thus Th17 cells.”
From T H 17 cells require ongoing classic IL-6 receptor signaling to retain transcriptional and functional identity (2020) · cites this paper as [3]
IL-6 together with TGFβ induces Th17 cells.
“IL-6 together with TGFβ induces Th17 cells (Fig. 2) (164).”
From IL-6 in inflammation, autoimmunity and cancer (2021) · cites this paper as [164]
Produced IL-6 further induces Th17 cell differentiation through STAT3 in the presence of TGFβ, IL-1β and IL-23, which are rich in inflammatory lesions and tumor microenvironments.
“The produced IL-6 further induces Th17 cell differentiation through STAT3 in the presence of TGFβ, IL-1β and IL-23, all of which are rich in inflammatory lesions and tumor microenvironments (164, 166, 169–171, 174, 175).”
From IL-6 in inflammation, autoimmunity and cancer (2021) · cites this paper as [164]
Th17 cells are an independent T helper cell subset.
“Th17 cells were established as an independent T helper cell subset with the discovery of signature cytokines IL-17A, IL-17F, and IL-22, lineage-specific differentiation factors, and dedicated or “master” transcription factors”
From TH17 cell heterogeneity and its role in tissue inflammation (2023) · cites this paper as [10]
In response to TGF-β in vitro as well as in vivo, many T cells co-express RORγt and Foxp3.
“In response to TGF-β in vitro as well as in vivo, many T cells co-express RORγt and Foxp3 (Veldhoen et al., 2006; Yang et al., 2008a).”
From Control of TH17/Treg Balance by Hypoxia-Inducible Factor 1 (2011) · cites this paper as Veldhoen et al., 2006

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Authors: Veldhoen, M., Hocking, R. J., Atkins, C. J., Locksley, R. M., & Stockinger, B.
Affiliations: National Institute for Medical Research (GB)
Howard Hughes Medical Institute (US)
Corresponding author: Stockinger, Brigitta
ORCID: Veldhoen, Marc
Locksley, Richard M.
Stockinger, Brigitta
Venue: Immunity
Publisher: Elsevier BV
Published: 2006-02
Volume: 24
Issue: 2
Pages: 179-189
ISSN: 1074-7613 (ISSN-L)
DOI: 10.1016/j.immuni.2006.01.001
OpenAlex: W2112866067
Cited by: 3,605
References: 70
Citations by year: 2026: 41 · 2025: 54 · 2024: 71 · 2023: 91 · 2022: 110 · 2021: 149 · 2020: 113 · 2019: 114 · 2018: 122 · 2017: 158 · 2016: 138 · 2015: 172 · 2014: 182 · 2013: 219 · 2012: 246
FWCI: 126.40
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 2759 d)
Locations: Immunity (publishedVersion)
PubMed (publishedVersion)
Funders: National Institute of Allergy and Infectious Diseases (AI30663, R01AI030663)
Topics: Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
Keywords: IL-17-producing T cells, TGF-β1, Th17 cell differentiation, regulatory T cells, interleukin-6, TLR3, TLR4, TLR9, IL-1β, TNF-α, IL-23, GATA3, T-bet, Smad7, Th1/Th2 differentiation, naive CD4+ T cells, inflammatory cytokines
MeSH terms: Animals, Cell Differentiation, Cells, Cultured, Dendritic Cells, Membrane Glycoproteins, Mice, Inbred C57BL, Mice, Transgenic, T-Lymphocytes, CD4-Positive T-Lymphocytes, Lymphocyte Subsets, Cytokines, Transforming Growth Factor beta, Receptors, Interleukin-1, Mice, Knockout, Th1 Cells, Th2 Cells, Interleukin-17, T-Lymphocytes, Regulatory, Mice, Smad7 Protein, Transforming Growth Factor beta1

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TGFβ in the Context of an Inflammatory Cytokine Milieu Supports De Novo Differentiation of IL-17-Producing T Cells

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