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

Danielle J. Smyth, Madeleine P. J. White, Chris J. C. Johnston, Anne-Marie Donachie, Marta Campillo Poveda, Henry J. McSorley, Rick M. Maizels (Lead / Corresponding author)

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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, transforming growth factor mimic (TGM), that functionally mimics the mammalian immunomodulatory cytokine TGF-β. HES and TGM showed a degree of protection in dextran sodium sulphate-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 trinitrobenzene sulphonic acid-induced model. However, in a T cell transfer-mediated model with recombination activation gene (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.

Original languageEnglish
Article numberkyad001
Number of pages12
JournalDiscovery Immunology
Volume2
Issue number1
Early online date18 Jan 2023
DOIs
Publication statusPublished - 2023

Keywords

  • dextran sodium sulphate
  • Heligmosomoides polygrus
  • inflammatory bowel disease

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