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A structurally distinct TGF-β mimic from an intestinal helminth parasite potently induces regulatory T cells

Author

Listed:
  • Chris J. C. Johnston

    (University of Edinburgh
    University of Edinburgh)

  • Danielle J. Smyth

    (University of Edinburgh
    University of Glasgow)

  • Ravindra B. Kodali

    (University of Pittsburgh School of Medicine)

  • Madeleine P. J. White

    (University of Glasgow)

  • Yvonne Harcus

    (University of Edinburgh)

  • Kara J. Filbey

    (University of Edinburgh
    Malaghan Institute of Medical Research)

  • James P. Hewitson

    (University of Edinburgh
    University of York)

  • Cynthia S. Hinck

    (University of Pittsburgh School of Medicine)

  • Alasdair Ivens

    (University of Edinburgh)

  • Andrea M. Kemter

    (University of Edinburgh)

  • Anna O. Kildemoes

    (University of Edinburgh
    University of Copenhagen)

  • Thierry Bihan

    (University of Edinburgh)

  • Dinesh C. Soares

    (University of Edinburgh)

  • Stephen M. Anderton

    (University of Edinburgh)

  • Thomas Brenn

    (University of Edinburgh)

  • Stephen J. Wigmore

    (University of Edinburgh)

  • Hannah V. Woodcock

    (University College London)

  • Rachel C. Chambers

    (University College London)

  • Andrew P. Hinck

    (University of Pittsburgh School of Medicine)

  • Henry J. McSorley

    (University of Edinburgh
    University of Edinburgh)

  • Rick M. Maizels

    (University of Glasgow)

Abstract

Helminth parasites defy immune exclusion through sophisticated evasion mechanisms, including activation of host immunosuppressive regulatory T (Treg) cells. The mouse parasite Heligmosomoides polygyrus can expand the host Treg population by secreting products that activate TGF-β signalling, but the identity of the active molecule is unknown. Here we identify an H. polygyrus TGF-β mimic (Hp-TGM) that replicates the biological and functional properties of TGF-β, including binding to mammalian TGF-β receptors and inducing mouse and human Foxp3+ Treg cells. Hp-TGM has no homology with mammalian TGF-β or other members of the TGF-β family, but is a member of the complement control protein superfamily. Thus, our data indicate that through convergent evolution, the parasite has acquired a protein with cytokine-like function that is able to exploit an endogenous pathway of immunoregulation in the host.

Suggested Citation

  • Chris J. C. Johnston & Danielle J. Smyth & Ravindra B. Kodali & Madeleine P. J. White & Yvonne Harcus & Kara J. Filbey & James P. Hewitson & Cynthia S. Hinck & Alasdair Ivens & Andrea M. Kemter & Anna, 2017. "A structurally distinct TGF-β mimic from an intestinal helminth parasite potently induces regulatory T cells," Nature Communications, Nature, vol. 8(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-01886-6
    DOI: 10.1038/s41467-017-01886-6
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