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

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  • Chris J. C. Johnston
  • Danielle J. Smyth
  • Ravindra B. Kodali
  • Madeleine P. J. White
  • Yvonne Harcus
  • Kara J. Filbey
  • Cynthia S. Hinck
  • Alasdair Ivens
  • Andrea M. Kemter
  • Anna O. Kildemoes
  • Thierry Le Bihan
  • Dinesh C. Soares
  • Stephen M. Anderton
  • Thomas Brenn
  • Stephen J. Wigmore
  • Hannah V. Woodcock
  • Rachel C. Chambers
  • Andrew P. Hinck
  • Henry J. McSorley
  • Rick M. Maizels


Publication details

JournalNature Communications
DateAccepted/In press - 23 Oct 2017
DatePublished (current) - 23 Nov 2017
Number of pages13
Original languageEnglish


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.

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© The Author(s) 2017

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