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

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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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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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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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