title: Regulation of Adenosine Deaminase on Induced Mouse Experimental Autoimmune Uveitis.
abstract: Adenosine is an important regulator of the immune response, and adenosine deaminase (ADA) inhibits this regulatory effect by converting adenosine into functionally inactive molecules. Studies showed that adenosine receptor agonists can be anti- or proinflammatory. Clarification of the mechanisms that cause these opposing effects should provide a better guide for therapeutic intervention. In this study, we investigated the effect of ADA on the development of experimental autoimmune uveitis (EAU) induced by immunizing EAU-prone mice with a known uveitogenic peptide, IRBP1-20. Our results showed that the effective time to administer a single dose of ADA to suppress induction of EAU was 8-14 d postimmunization, shortly before EAU expression; however, ADA treatment at other time points exacerbated disease. ADA preferentially inhibited Th17 responses, and this effect was γδ T cell dependent. Our results demonstrated that the existing immune status strongly influences the anti- or proinflammatory effects of ADA. Our observations should help to improve the design of ADA- and adenosine receptor-targeted therapies.
authors: Doheny Eye Institute, Department of Ophthalmology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90033;
authors: Dongchun
authors: D
authors: Liang
authors: Doheny Eye Institute, Department of Ophthalmology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90033;
authors: Aijun
authors: A
authors: Zuo
authors: Doheny Eye Institute, Department of Ophthalmology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90033; Department of Medical Laboratory, Key Laboratory of Clinical Laboratory Diagnostics, University of Shandong, Weifang Medical University, Weifang, Shandong 261053, China; and.
authors: Ronglan
authors: http://orcid.org/0000-0002-4302-2563
authors: R
authors: Zhao
authors: Department of Ophthalmology and Visual Sciences, Kentucky Lions Eye Center, University of Louisville, Louisville, KY 40202.
authors: Hui
authors: H
authors: Shao
authors: Department of Ophthalmology and Visual Sciences, Kentucky Lions Eye Center, University of Louisville, Louisville, KY 40202.
authors: Henry J
authors: HJ
authors: Kaplan
authors: Doheny Eye Institute, Department of Ophthalmology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90033; dsun@doheny.org.
authors: Deming
authors: http://orcid.org/0000-0003-4851-0416
authors: D
authors: Sun
mesh_terms: D000243:Adenosine Deaminase / Q000008:administration & dosage*; D000818:Animals; D001327:Autoimmune Diseases / Q000188:drug therapy* / Q000276:immunology; D002478:Cells, Cultured; D005136:Eye Proteins / Q000276:immunology; D005260:Female; D006801:Humans; D007114:Immunization; D007155:Immunologic Factors / Q000008:administration & dosage*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D023421:Models, Animal; D058990:Molecular Targeted Therapy; D010446:Peptide Fragments / Q000276:immunology; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000235:genetics / Q000378:metabolism; D012177:Retinol-Binding Proteins / Q000276:immunology; D058504:Th17 Cells / Q000187:drug effects* / Q000276:immunology; D014605:Uveitis / Q000188:drug therapy* / Q000276:immunology; D000099214:Retinol-Binding Proteins, Interstitial
chemical_list: D000243:Adenosine Deaminase; D005136:Eye Proteins; D007155:Immunologic Factors; D010446:Peptide Fragments; D016692:Receptors, Antigen, T-Cell, gamma-delta; D012177:Retinol-Binding Proteins; D000099214:Retinol-Binding Proteins, Interstitial