Journal article

The parasite cytokine mimic Hp-TGM potently replicates the regulatory effects of TGF-β on murine CD4 T cells

MPJ White, DJ Smyth, L Cook, SF Ziegler, MK Levings, RM Maizels

Immunology and Cell Biology | WILEY | Published : 2021

Abstract

Transforming growth factor-beta (TGF-β) family proteins mediate many vital biological functions in growth, development and regulation of the immune system. TGF-β itself controls immune homeostasis and inflammation, including conversion of naïve CD4+ T cells into Foxp3+ regulatory T cells (Tregs) in the presence of interleukin-2 and T-cell receptor ligands. The helminth parasite Heligmosomoides polygyrus exploits this pathway through a structurally novel TGF-β mimic (Hp-TGM), which binds to mammalian TGF-β receptors and induces Tregs. Here, we performed detailed comparisons of Hp-TGM with mammalian TGF-β. Compared with TGF-β, Hp-TGM induced greater numbers of Foxp3+ Tregs (iTregs), with more ..

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University of Melbourne Researchers

Grants

Awarded by Kenneth Rainin Foundation


Funding Acknowledgements

We thank Nicola Britton and Claire Ciancia for excellent technical assistance. The authors gratefully acknowledge the Flow Core Facility, University of Glasgow for their support and assistance as well as BD Biosciences for their panel design expertise. We thank Jana Gillies for her help in running and designing the mouse TSDR assay, and Andy Hinck for his critical comments on the manuscript. This work was supported by the Kenneth Rainin Foundation through Synergy and Innovator Grants (Refs 2015-964 and 2016-3067), the Wellcome Trust through an Investigator Award to RMM (Ref 106122), the Wellcome Trust core-funded Wellcome Centre for Integrative Parasitology (Ref: 104111) and by the Medical Research Council Confidence-in-Concept scheme. MKL and LC received salary awards from the BC Children's Hospital Research Institute.