title: ITE, a novel endogenous nontoxic aryl hydrocarbon receptor ligand, efficiently suppresses EAU and T-cell-mediated immunity.
abstract: OBJECTIVE
  Ligands for aryl hydrocarbon receptor (AHR), such as dioxins, are highly toxic. One such ligand, TCDD, was found to exert potent immunosuppressive capacities in mice developing pathogenic autoimmune processes, including EAU, but its toxicity makes it unusable for humans. A recently identified endogenous AHR ligand, ITE, is also immunosuppressive, but is nontoxic and could therefore be useful for therapy in humans. Here, we tested ITE for its capacity to inhibit EAU and related immune responses.
  
  
  METHODS
  EAU was induced in B10.A mice by immunization with interphotoreceptor retinoid-binding protein (IRBP; 40 μg) in CFA. Treatment with ITE was by daily intraperitoneal injection of 0.2 mg. Disease severity was assessed by both fundoscopy and histological examination. Draining lymph node cells were tested for proliferation by thymidine uptake and for cytokine production and release by ELISA. In addition, the intracellular expression of cytokines and Foxp3 was determined by flow cytometry. Serum antibodies were measured by ELISA.
  
  
  RESULTS
  Treatment with ITE efficiently inhibited the development of EAU in mice, as well as the cellular immune responses against IRBP and PPD. ITE treatment inhibited the expansion of both Th1 and Th17 subpopulations, as well as their release of the signature cytokines, IFN-gamma and IL-17. The treatment moderately increased, however, the proportion of Foxp3 expressing T-regulatory cells. Antibody production was not affected by the treatment.
  
  
  CONCLUSIONS
  ITE, an endogenous AHR ligand, efficiently inhibits EAU development and related cellular immune responses. Being nontoxic, ITE may be considered for treatment of pathogenic immunity in humans.
authors.affiliation: Experimental Immunology Section, Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Lindsey F
authors.initials: LF
authors.lastname: Nugent
authors.forename: Guangpu
authors.initials: G
authors.lastname: Shi
authors.forename: Barbara P
authors.initials: BP
authors.lastname: Vistica
authors.forename: Osato
authors.initials: O
authors.lastname: Ogbeifun
authors.forename: Samuel J H
authors.initials: SJ
authors.lastname: Hinshaw
authors.forename: Igal
authors.initials: I
authors.lastname: Gery
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D002454:Cell Differentiation / Q000276:immunology; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005136:Eye Proteins / Q000276:immunology / Q000378:metabolism*; D005260:Female; D005434:Flow Cytometry; D007111:Immunity, Cellular / Q000276:immunology*; D051379:Mice; D012177:Retinol-Binding Proteins / Q000276:immunology / Q000378:metabolism*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000473:pathology; D014605:Uveitis / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D000099214:Retinol-Binding Proteins, Interstitial
chemical_list: D016207:Cytokines; D005136:Eye Proteins; D012177:Retinol-Binding Proteins; D000099214:Retinol-Binding Proteins, Interstitial
keywords: T-cell mediated immunity; aryl hydrocarbon receptor ligand; experimental autoimmune uveitis