title: An A2B Adenosine Receptor Agonist Promotes Th17 Autoimmune Responses in Experimental Autoimmune Uveitis (EAU) via Dendritic Cell Activation.
abstract: We have recently reported that, although adenosine receptor (AR) agonists have a suppressive effect on Th1 autoreactive T cells, their effect on Th17 autoreactive T cells and γδ T cells is stimulatory and this effect is mainly mediated via A2A adenosine receptors (A2ARs). In this study, we further demonstrate that treatment of C57BL/6 (B6) mice with a selective A2B adenosine receptor (A2BR) agonist greatly enhanced the development of experimental autoimmune uveitis (EAU), whereas treatment with an A2BR antagonist significantly ameliorated severity of EAU. The A2BR agonist-treated mice showed augmented Th17, but not Th1, responses. Mechanistic studies showed that the A2BR agonist-induced enhancement of the Th17 response was significantly lower when TCR-δ-/- mice received the same treatment and that transfer of γδ T cells into TCR-δ-/- mice partially restored this effect. We also showed that dendritic cells (DCs) from A2BR agonist-treated mice showed a significantly increased ability to activate γδ T cells and Th17 autoreactive T cells. Thus, our previous studies have shown that, in EAU, activated γδ T cells possess greatly increased ability to enhance Th17 autoimmune responses. In the present study, we showed that exposure of DCs to A2BR agonist facilitated γδ T cell activation, leading to augmented Th17 responses and progressive EAU development. Our results further support our previous finding that AR agonists have distinct effects on Th1 and Th17 autoimmune responses.
authors.affiliation: Doheny Eye Institute and Department of Ophthalmology, University of California, Los Angeles, CA90033, United States of America.
authors.forename: Mingjiazi
authors.initials: M
authors.lastname: Chen
authors.affiliation: Doheny Eye Institute and Department of Ophthalmology, University of California, Los Angeles, CA90033, United States of America.
authors.forename: Dongchun
authors.initials: D
authors.lastname: Liang
authors.affiliation: Doheny Eye Institute and Department of Ophthalmology, University of California, Los Angeles, CA90033, United States of America.
authors.forename: Aijun
authors.initials: A
authors.lastname: Zuo
authors.affiliation: Department of Ophthalmology and Visual Sciences, Kentucky Lions Eye Center, University of Louisville, Louisville, KY40202, United States of America.
authors.forename: Hui
authors.initials: H
authors.lastname: Shao
authors.affiliation: Department of Ophthalmology and Visual Sciences, Kentucky Lions Eye Center, University of Louisville, Louisville, KY40202, United States of America.
authors.forename: Henry J
authors.initials: HJ
authors.lastname: Kaplan
authors.affiliation: Doheny Eye Institute and Department of Ophthalmology, University of California, Los Angeles, CA90033, United States of America.
authors.forename: Deming
authors.initials: D
authors.lastname: Sun
mesh_terms: D058908:Adenosine A2 Receptor Agonists / Q000494:pharmacology*; D000818:Animals; D001327:Autoimmune Diseases / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D003713:Dendritic Cells / Q000276:immunology* / Q000473:pathology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D043704:Receptor, Adenosine A2B / Q000235:genetics / Q000276:immunology*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000235:genetics / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology / Q000473:pathology; D058504:Th17 Cells / Q000276:immunology* / Q000473:pathology; D014605:Uveitis / Q000235:genetics / Q000276:immunology* / Q000473:pathology
chemical_list: D058908:Adenosine A2 Receptor Agonists; D043704:Receptor, Adenosine A2B; D016692:Receptors, Antigen, T-Cell, gamma-delta