Induction of stable human FOXP3+ Tregs by a parasite‐derived TGF‐β mimic

• DOI: 10.1111/imcb.12475
• Publication Date: 2021-04-30T13:19:20Z
• Authors: Laura Cook; Kyle T Reid; Elmeri Häkkinen; Brett de Bie; Shigeru Tanaka; Danielle J Smyth; Madeleine PJ White; May Q Wong; Qing Huang; Jana K Gillies; Steven F. Ziegler; Rick M Maizels; Megan K Levings
• Keywords: Regulatory T cell; Proinflammatory cytokine; Heligmosomoides polygyrus

Immune homeostasis in the intestine is tightly controlled by FOXP3+ regulatory T cells (Tregs), defects of which are linked to development chronic conditions, such as inflammatory bowel disease (IBD). As a mechanism immune evasion, several species intestinal parasites boost Treg activity. The parasite Heligmosomoides polygyrus known secrete molecule (Hp-TGM) that mimics ability TGF-β induce FOXP3 expression CD4+ cells. study aimed investigate whether Hp-TGM could human Tregs potential therapeutic approach for diseases. from healthy volunteers were expanded presence or TGF-β. induction was measured flow cytometric detection and other markers, CD25 CTLA-4. Epigenetic changes detected using ChIP-Seq pyrosequencing FOXP3. phenotype stability assessed following cytokine challenge function evaluated cellular co-culture suppression assays bead arrays secreted cytokines. efficiently induced (> 60%), addition CTLA-4, caused epigenetic modification locus greater extent than Hp-TGM-induced had superior suppressive compared with TGF-β-induced Tregs, retained their exposure Furthermore, Treg-like vivo differentiated Th1 Th17 cells, indicating its re-program memory enhance tolerance. These data indicate has be used generate stable treat IBD