A novel aryl hydrocarbon receptor ligand, ITE, suppresses immune-mediated ocular inflammation

Wednesday, October 26, 2011 — Poster Session IV
2:00 p.m. – 4:00 p.m.	Natcher Conference Center	NEI	IMMUNO/INFLAM-22

Authors

• L Nugent
• G Shi
• C Tan
• B Vistica
• I Gery

Abstract

Activation of the ligand-activated transcription factor aryl hydrocarbon receptor (AHR) by its endogenous ligand, ITE, suppresses experimental autoimmune encephalomyelitis (EAE) by expanding CD25+Foxp3+ Treg cells and interfering with the activation of Th1 and Th17 cells. We investigated the suppressive effects of ITE on the induction of experimental autoimmune uveitis (EAU), a model of uveitis in humans. B10.A mice were immunized with an 0.2ml emulsion of 40μg interphotoreceptor retinoid-binding protein (IRBP) in CFA (s.c. injection) and concurrently injected with 0.2μg pertussis toxin (i.p.). Mice were injected daily (i.p.) with 200μg of ITE or PBS (“control”) for 14 days. Mice were evaluated for the development of EAU by fundoscopy on day 12 post-immunization for clinical changes and by histological examination on day 14. Draining lymph node cells were cultured with IRBP to measure proliferative response and cytokine secretion. Serum antibody to IRBP was measured by ELISA. Both clinical and pathological evaluations revealed that ITE suppressed EAU. Additionally, ITE suppressed the T-cell recall proliferative response to IRBP, slightly decreased the antibody response, and decreased the secretion of both pro-inflammatory (IFNγ, IL-17) and immunoregulatory (IL-10) cytokines. Thus, nontoxic endogenous AHR ligands like ITE are potential new compounds for the treatment of autoimmune disorders.

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