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- Title
A structurally distinct TGF-β mimic from an intestinal helminth parasite potently induces regulatory T cells.
- Authors
Johnston, Chris J. C.; Smyth, Danielle J.; Kodali, Ravindra B.; White, Madeleine P. J.; Harcus, Yvonne; Filbey, Kara J.; Hewitson, James P.; Hinck, Cynthia S.; Ivens, Alasdair; Kemter, Andrea M.; Kildemoes, Anna O.; Le Bihan, Thierry; Soares, Dinesh C.; Anderton, Stephen M.; Brenn, Thomas; Wigmore, Stephen J.; Woodcock, Hannah V.; Chambers, Rachel C.; Hinck, Andrew P.; McSorley, Henry J.
- 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.
- Publication
Nature Communications, 2017, Vol 8, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-017-01886-6