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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