Protection from T cell-dependent colitis by the helminth-derived immunomodulatory mimic of transforming growth factor-ß, Hp-TGM

Smyth, D. J. , White, M. P.J., Johnston, C. J.C., Donachie, A.-M., Campillo Poveda, M. , McSorley, H. J. and Maizels, R. M. (2023) Protection from T cell-dependent colitis by the helminth-derived immunomodulatory mimic of transforming growth factor-ß, Hp-TGM. Discovery Immunology, 2(1), kyad001. (doi: 10.1093/discim/kyad001) (PMID:36855464) (PMCID:PMC9958376)

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Abstract

In animal models of inflammatory colitis, pathology can be ameliorated by several intestinal helminth parasites, including the mouse nematode Heligmosomoides polygyrus. To identify parasite products that may exert anti-inflammatory effects in vivo, we tested H. polygyrus excretory-secretory (HES) products, as well as a recombinantly-expressed parasite protein, TGM, that functionally mimics the mammalian immunomodulatory cytokine TGF-β. HES and TGM showed a degree of protection in DSS-induced colitis, with a reduction in inflammatory cytokines, but did not fully block the development of pathology. HES also showed little benefit in a similar acute TNBS-induced model. However, in a T cell transfer-mediated model with RAG-deficient mice, HES reduced disease scores if administered throughout the first 2 or 4 weeks following transfer but was less effective if treatment was delayed until 14 days after T cell transfer. Recombinant TGM similarly dampened colitis in RAG-deficient recipients of effector T cells, and was effective even if introduced only once symptoms had begun to be manifest. These results are a promising indication that TGM may replicate, and even surpass, the modulatory properties of native parasite HES.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Donachie, Ms Anne Marie and Campillo Poveda, Dr Marta and White, Dr Madeleine and Maizels, Professor Rick and Smyth, Dr Danielle
Authors: Smyth, D. J., White, M. P.J., Johnston, C. J.C., Donachie, A.-M., Campillo Poveda, M., McSorley, H. J., and Maizels, R. M.
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity
Research Centre:College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Immunobiology
Journal Name:Discovery Immunology
Publisher:Oxford University Press
ISSN:2754-2483
ISSN (Online):2754-2483
Published Online:18 January 2023
Copyright Holders:Copyright © 2023 The Authors
First Published:First published in Discovery Immunology 2(1): kyad001
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
173801Helminths and the Immune System: Regulation, Regulators and ImmunityRichard MaizelsWellcome Trust (WELLCOTR)106122/A/14/ZInstitute of Infection, Immunity & Inflammation
308411Molecular and Cellular Interactions in Helminth InfectionsRichard MaizelsWellcome Trust (WELLCOTR)219530/Z/19/ZIII - Parasitology
170547The Wellcome Centre for Molecular Parasitology ( Core Support )Andrew WatersWellcome Trust (WELLCOTR)104111/Z/14/ZIII - Parasitology