title: Both MC5r and A2Ar are required for protective regulatory immunity in the spleen of post-experimental autoimmune uveitis in mice.
abstract: The ocular microenvironment uses a poorly defined mela5 receptor (MC5r)-dependent pathway to recover immune tolerance following intraocular inflammation. This dependency is seen in experimental autoimmune uveoretinitis (EAU), a mouse model of endogenous human autoimmune uveitis, with the emergence of autoantigen-specific regulatory immunity in the spleen that protects the mice from recurrence of EAU. In this study, we found that the MC5r-dependent regulatory immunity increased CD11b(+)F4/80(+)Ly-6C(low)Ly-6G(+)CD39(+)CD73(+) APCs in the spleen of post-EAU mice. These MC5r-dependent APCs require adenosine 2A receptor expression on T cells to activate EAU-suppressing CD25(+)CD4(+)Foxp3(+) regulatory T cells. Therefore, in the recovery from autoimmune disease, the ocular microenvironment induces tolerance through a melanocortin-mediated expansion of Ly-6G(+) regulatory APCs in the spleen that use the adenosinergic pathway to promote activation of autoantigen-specific regulatory T cells.
authors.affiliation: Department of Ophthalmology, Boston University School of Medicine, Boston, MA 02118.
authors.forename: Darren J
authors.initials: DJ
authors.lastname: Lee
authors.forename: Andrew W
authors.initials: AW
authors.lastname: Taylor
mesh_terms: D015720:5'-Nucleotidase / Q000378:metabolism; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D000950:Antigens, Ly / Q000378:metabolism; D001081:Apyrase / Q000378:metabolism; D001324:Autoantigens / Q000276:immunology; D001327:Autoimmune Diseases; D039481:CD11b Antigen / Q000378:metabolism; D015704:CD4 Antigens / Q000378:metabolism; D004195:Disease Models, Animal; D005123:Eye / Q000276:immunology; D005136:Eye Proteins / Q000276:immunology; D051858:Forkhead Transcription Factors / Q000378:metabolism; D007249:Inflammation / Q000276:immunology; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D043705:Receptor, Adenosine A2A / Q000378:metabolism*; D044101:Receptors, Melanocortin / Q000235:genetics / Q000378:metabolism*; D012177:Retinol-Binding Proteins / Q000276:immunology; D017634:Self Tolerance / Q000276:immunology*; D013154:Spleen / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism; D014605:Uveitis / Q000276:immunology*; D000099214:Retinol-Binding Proteins, Interstitial
chemical_list: D015720:5'-Nucleotidase; D015703:Antigens, CD; D000950:Antigens, Ly; D001081:Apyrase; D001324:Autoantigens; D039481:CD11b Antigen; D015704:CD4 Antigens; D005136:Eye Proteins; D051858:Forkhead Transcription Factors; D053645:Interleukin-2 Receptor alpha Subunit; D043705:Receptor, Adenosine A2A; D044101:Receptors, Melanocortin; D012177:Retinol-Binding Proteins; D000099214:Retinol-Binding Proteins, Interstitial; C498833:Foxp3 protein, mouse; C526827:Ly6 protein, mouse; C086971:melanocortin 5 receptor; C067869:CD39 antigen
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