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TNF-α blockade induces IL-10 expression in human CD4+ T cells

Author

Listed:
  • Hayley G. Evans

    (Centre for Molecular and Cellular Biology of Inflammation (CMCBI), Infection and Inflammatory Disease, King’s College London
    Present address: Nuffield Department of Clinical Neurosciences, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford OX3 9DS, UK)

  • Urmas Roostalu

    (Centre for Molecular and Cellular Biology of Inflammation (CMCBI), Infection and Inflammatory Disease, King’s College London
    Present address: Institute of Inflammation and Repair, Michael Smith Bldg, Oxford Road, University of Manchester, Manchester M13 9PL, UK)

  • Gina J. Walter

    (Centre for Molecular and Cellular Biology of Inflammation (CMCBI), Infection and Inflammatory Disease, King’s College London)

  • Nicola J. Gullick

    (Centre for Molecular and Cellular Biology of Inflammation (CMCBI), Infection and Inflammatory Disease, King’s College London
    Present address: Department of Rheumatology, King’s College Hospital NHS Trust, London SE5 9RS, UK)

  • Klaus S. Frederiksen

    (Biopharmaceuticals Research Unit, Inflammation Biology, Novo Nordisk A/S)

  • Ceri A. Roberts

    (Centre for Molecular and Cellular Biology of Inflammation (CMCBI), Infection and Inflammatory Disease, King’s College London)

  • Jonathan Sumner

    (Centre for Molecular and Cellular Biology of Inflammation (CMCBI), Infection and Inflammatory Disease, King’s College London)

  • Dominique L. Baeten

    (Academic Medical Centre/University of Amsterdam)

  • Jens G. Gerwien

    (Biopharmaceuticals Research Unit, Inflammation Biology, Novo Nordisk A/S)

  • Andrew P. Cope

    (Centre for Molecular and Cellular Biology of Inflammation (CMCBI), Infection and Inflammatory Disease, King’s College London
    King's College London)

  • Frederic Geissmann

    (Centre for Molecular and Cellular Biology of Inflammation (CMCBI), Infection and Inflammatory Disease, King’s College London)

  • Bruce W. Kirkham

    (Guy’s and St Thomas’ NHS Trust)

  • Leonie S. Taams

    (Centre for Molecular and Cellular Biology of Inflammation (CMCBI), Infection and Inflammatory Disease, King’s College London)

Abstract

IL-17+ CD4+ T (Th17) cells contribute to the pathogenesis of several human inflammatory diseases. Here we demonstrate that TNF inhibitor (TNFi) drugs induce the anti-inflammatory cytokine IL-10 in CD4+ T cells including IL-17+ CD4+ T cells. TNFi-mediated induction of IL-10 in IL-17+ CD4+ T cells is Treg-/Foxp3-independent, requires IL-10 and is overcome by IL-1β. TNFi-exposed IL-17+ CD4+ T cells are molecularly and functionally distinct, with a unique gene signature characterized by expression of IL10 and IKZF3 (encoding Aiolos). We show that Aiolos binds conserved regions in the IL10 locus in IL-17+ CD4+ T cells. Furthermore, IKZF3 and IL10 expression levels correlate in primary CD4+ T cells and Aiolos overexpression is sufficient to drive IL10 in these cells. Our data demonstrate that TNF-α blockade induces IL-10 in CD4+ T cells including Th17 cells and suggest a role for the transcription factor Aiolos in the regulation of IL-10 in CD4+ T cells.

Suggested Citation

  • Hayley G. Evans & Urmas Roostalu & Gina J. Walter & Nicola J. Gullick & Klaus S. Frederiksen & Ceri A. Roberts & Jonathan Sumner & Dominique L. Baeten & Jens G. Gerwien & Andrew P. Cope & Frederic Gei, 2014. "TNF-α blockade induces IL-10 expression in human CD4+ T cells," Nature Communications, Nature, vol. 5(1), pages 1-12, May.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms4199
    DOI: 10.1038/ncomms4199
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