title: CD73 Expressed on γδ T Cells Shapes Their Regulatory Effect in Experimental Autoimmune Uveitis.
abstract: γδ T cells can either enhance or inhibit an adaptive immune response, but the mechanisms involved are not fully understood. Given that CD73 is the main enzyme responsible for conversion of AMP into the immunosuppressive molecule adenosine, we investigated its role in the regulatory function of γδ T cells in experimental autoimmune uveitis (EAU). We found that γδ T cells expressed different amounts of CD73 during the different stages of EAU and that low CD73 expression on γδ T cells correlated with enhanced Th17 response-promoting activity. Functional comparison of CD73-deficient and wild-type B6 (CD73+/+) mice showed that failure to express CD73 decreased both the enhancing and suppressive effects of γδ T cells on EAU. We also demonstrated that γδ T cells expressed different amounts of CD73 when activated by different pathways, which enabled them to either enhance or inhibit an adaptive immune response. Our results demonstrate that targeting CD73 expression on γδ T cells may allow us to manipulate their pro- or anti-inflammatory effect on Th17 responses.
authors.affiliation: Doheny Eye Institute and Department of Ophthalmology, David Geffen School of Medicine at UCLA, Los Angeles, California 90033, United States of America.
authors.forename: Dongchun
authors.initials: D
authors.lastname: Liang
authors.affiliation: Doheny Eye Institute and Department of Ophthalmology, David Geffen School of Medicine at UCLA, Los Angeles, California 90033, United States of America.
authors.forename: Aijun
authors.initials: A
authors.lastname: Zuo
authors.affiliation: Doheny Eye Institute and Department of Ophthalmology, David Geffen School of Medicine at UCLA, Los Angeles, California 90033, United States of America.|Department of Medical Laboratory, Key Laboratory of Clinical Laboratory Diagnostics in University of Shandong, Weifang Medical University, Weifang 261053, Shandong, China.
authors.forename: Ronglan
authors.initials: R
authors.lastname: Zhao
authors.affiliation: Department of Ophthalmology and Visual Sciences, Kentucky Lions Eye Center, University of Louisville, Louisville, Kentucky 40202, United States of America.
authors.forename: Hui
authors.initials: H
authors.lastname: Shao
authors.affiliation: Department of Biomedical Research, National Jewish Health, Denver, Colorado 80206, United States of America.
authors.forename: Willi K
authors.initials: WK
authors.lastname: Born
authors.affiliation: Department of Biomedical Research, National Jewish Health, Denver, Colorado 80206, United States of America.
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: O'Brien
authors.affiliation: Department of Ophthalmology and Visual Sciences, Kentucky Lions Eye Center, University of Louisville, Louisville, Kentucky 40202, United States of America.
authors.forename: Henry J
authors.initials: HJ
authors.lastname: Kaplan
authors.affiliation: Doheny Eye Institute and Department of Ophthalmology, David Geffen School of Medicine at UCLA, Los Angeles, California 90033, United States of America.
authors.forename: Deming
authors.initials: D
authors.lastname: Sun
mesh_terms: D015720:5'-Nucleotidase / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D000241:Adenosine / Q000378:metabolism; D000249:Adenosine Monophosphate / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology; D005136:Eye Proteins / Q000276:immunology / Q000633:toxicity; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology; D007371:Interferon-gamma / Q000097:blood / Q000172:deficiency; D020381:Interleukin-17 / Q000097:blood; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020721:Nervous System Autoimmune Disease, Experimental / Q000201:enzymology / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology / Q000633:toxicity; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000032:analysis / Q000172:deficiency; D012177:Retinol-Binding Proteins / Q000276:immunology / Q000633:toxicity; D016176:T-Lymphocyte Subsets / Q000201:enzymology / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000201:enzymology / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D058504:Th17 Cells / Q000276:immunology; D014605:Uveitis / Q000201:enzymology / Q000276:immunology*; D000099214:Retinol-Binding Proteins, Interstitial
chemical_list: D015720:5'-Nucleotidase; D000241:Adenosine; D000249:Adenosine Monophosphate; D005136:Eye Proteins; D007371:Interferon-gamma; D020381:Interleukin-17; D010446:Peptide Fragments; D016692:Receptors, Antigen, T-Cell, gamma-delta; D012177:Retinol-Binding Proteins; D000099214:Retinol-Binding Proteins, Interstitial