Indoleamine 2,3-dioxygenase-dependent expansion of T-regulatory cells maintains mucosal healing in ulcerative colitis

Therapeutic Advances in Gastroenterology
Aleksandar AcovicVladislav Volarevic

Abstract

Dendritic cell (DC)-derived indolamine 2,3-dioxygenase (IDO) degrades tryptophan to kynurenine, which promotes conversion of inflammatory T cells in immunosuppressive regulatory T cells (Tregs). We analyzed the significance of the IDO:Treg axis for inducing and maintaining mucosal healing in ulcerative colitis (UC). Dextran sodium sulphate (DSS)-induced colitis in BALB/c mice (model for mucosal healing) and C57BL/6 mice (model for persistent disease) was used. Serum, fecal samples and colon-infiltrating immune cells of 65 patients with UC with mucosal healing or persistent colitis were analyzed. Significantly higher serum levels of kynurenine and downregulated inflammatory cytokines were noticed in DSS-treated BALB/c mice compared with C57BL/6 mice. Increased IDO activity and attenuated capacity for antigen presentation and production of inflammatory cytokines, observed in BALB/c DCs, was followed by a significantly lower number of inflammatory T helper 1 (Th1) and Th17 cells and a notably increased number of Tregs in the colons of DSS-treated BALB/c mice. DCs and Tregs were crucially important for the maintenance of mucosal healing since their depletion aggravated colitis. Mucosal healing, followed by an increase in kynurenine...Continue Reading

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Citations

Dec 24, 2018·Therapeutic Advances in Gastroenterology·Aleksandar AcovicVladislav Volarevic
Mar 21, 2020·Frontiers in Immunology·Imane NafiaAntoine Italiano
Dec 5, 2019·World Journal of Gastroenterology : WJG·Marina JovanovicNatasa Zdravkovic
Feb 23, 2021·Molecular Therapy Oncolytics·Yixiao QinYongyan Wu
Jun 3, 2021·International Journal of Molecular Sciences·Maria NamwanjeAmandeep Bajwa
Jul 13, 2021·The Tohoku Journal of Experimental Medicine·Marina Milun JovanovicMilan Milorad Jovanovic

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Methods Mentioned

BETA
enzyme-linked immunosorbent assay
ELISA
flow cytometry
density gradient centrifugation
PMA

Software Mentioned

SPSS
Flowing

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