Abstract
In oral tolerance, locally instigated tolerance in the gut propagate to systemic tolerance. In order to investigate the mechanism, we analyzed indoleamine 2,3-dioxygenase (IDO) expression in splenic dendritic cell (DC) subsets and tested whether DCs suppress collagen-induced arthritis (CIA) by inducing regulatory T cells (Tregs). The proportion of IDO-expressing cells was higher in the CD11b+ subset of splenic DCs from orally tolerized CIA mice. These DCs suppressed type II collagen-specific T cell proliferation and promoted Treg induction from CD4+CD25- T cells using transforming growth factor-β. These DCs also increased the expression of cytotoxic T lymphocyte antigen-4 and programmed death-1 on Tregs. When adoptively transferred, spenic IDO-expressing CD11b+ DCs from tolerized animals suppressed the development of arthritis, increased the Treg/Th17 cell ratio, and decreased the production of inflammatory cytokines in the spleen. Taken together, a distinct subset of splenic IDO+CD11b+DCs is responsible for the systemic immune regulation in oral tolerance.
Original language | English (US) |
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Pages (from-to) | 45-54 |
Number of pages | 10 |
Journal | Cellular Immunology |
Volume | 278 |
Issue number | 1-2 |
DOIs | |
State | Published - Jul 2012 |
Keywords
- Collagen-induced arthritis
- Dendritic cell
- Indoleamine 2,3-dioxygenase
- Oral tolerance
- Regulatory T cell
- Spleen
ASJC Scopus subject areas
- Immunology