A structurally distinct TGF-β mimic from an intestinal helminth parasite potently induces regulatory T cells
Open Access
- 23 November 2017
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Communications
- Vol. 8 (1), 1-13
- https://doi.org/10.1038/s41467-017-01886-6
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.This publication has 68 references indexed in Scilit:
- TGF-β signalling is mediated by two autonomously functioning TβRI:TβRII pairsThe EMBO Journal, 2011
- Helminth secretions induce de novo T cell Foxp3 expression and regulatory function through the TGF-β pathwayThe Journal of Experimental Medicine, 2010
- Ternary Complex of Transforming Growth Factor-β1 Reveals Isoform-specific Ligand Recognition and Receptor Recruitment in the SuperfamilyOnline Journal of Public Health Informatics, 2010
- TGF-β: A Master of All T Cell TradesCell, 2008
- Molecular Antagonism and Plasticity of Regulatory and Inflammatory T Cell ProgramsImmunity, 2008
- TGF-β-induced Foxp3 inhibits TH17 cell differentiation by antagonizing RORγt functionNature, 2008
- Expansion and activation of CD4+CD25+ regulatory T cells in Heligmosomoides polygyrus infectionEuropean Journal of Immunology, 2007
- Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cellsNature, 2006
- Immune Regulation by helminth parasites: cellular and molecular mechanismsNature Reviews Immunology, 2003
- TGFβ-related pathways: roles in Caenorhabditis elegans developmentTrends in Genetics, 2000