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Induction of stable human FOXP3 + Tregs by a parasite-derived TGF-β mimic.
- Source :
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Immunology and cell biology [Immunol Cell Biol] 2021 Sep; Vol. 99 (8), pp. 833-847. Date of Electronic Publication: 2021 Jun 03. - Publication Year :
- 2021
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Abstract
- Immune homeostasis in the intestine is tightly controlled by FOXP3 <superscript>+</superscript> regulatory T cells (Tregs), defects of which are linked to the development of chronic conditions, such as inflammatory bowel disease (IBD). As a mechanism of immune evasion, several species of intestinal parasites boost Treg activity. The parasite Heligmosomoides polygyrus is known to secrete a molecule (Hp-TGM) that mimics the ability of TGF-β to induce FOXP3 expression in CD4 <superscript>+</superscript> T cells. The study aimed to investigate whether Hp-TGM could induce human FOXP3 <superscript>+</superscript> Tregs as a potential therapeutic approach for inflammatory diseases. CD4 <superscript>+</superscript> T cells from healthy volunteers were expanded in the presence of Hp-TGM or TGF-β. Treg induction was measured by flow cytometric detection of FOXP3 and other Treg markers, such as CD25 and CTLA-4. Epigenetic changes were detected using ChIP-Seq and pyrosequencing of FOXP3. Treg phenotype stability was assessed following inflammatory cytokine challenge and Treg function was evaluated by cellular co-culture suppression assays and cytometric bead arrays for secreted cytokines. Hp-TGM efficiently induced FOXP3 expression (> 60%), in addition to CD25 and CTLA-4, and caused epigenetic modification of the FOXP3 locus to a greater extent than TGF-β. Hp-TGM-induced Tregs had superior suppressive function compared with TGF-β-induced Tregs, and retained their phenotype following exposure to inflammatory cytokines. Furthermore, Hp-TGM induced a Treg-like phenotype in in vivo differentiated Th1 and Th17 cells, indicating its potential to re-program memory cells to enhance immune tolerance. These data indicate Hp-TGM has potential to be used to generate stable human FOXP3 <superscript>+</superscript> Tregs to treat IBD and other inflammatory diseases.<br /> (© 2021 The Authors. Immunology & Cell Biology published by John Wiley & Sons Australia, Ltd on behalf of Australian and New Zealand Society for Immunology, Inc.)
Details
- Language :
- English
- ISSN :
- 1440-1711
- Volume :
- 99
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- Immunology and cell biology
- Publication Type :
- Academic Journal
- Accession number :
- 33929751
- Full Text :
- https://doi.org/10.1111/imcb.12475