title: Galectin-8 Ameliorates Murine Autoimmune Ocular Pathology and Promotes a Regulatory T Cell Response.
abstract: Galectins have emerged as potent immunoregulatory agents that control chronic inflammation through distinct mechanisms. Here, we report that treatment with Galectin-8 (Gal-8), a tandem-repeat member of the galectin family, reduces retinal pathology and prevents photoreceptor cell damage in a murine model of experimental autoimmune uveitis. Gal-8 treatment increased the number of regulatory T cells (Treg) in both the draining lymph node (dLN) and the inflamed retina. Moreover, a greater percentage of Treg cells in the dLN and retina of Gal-8 treated animals expressed the inhibitory coreceptor cytotoxic T lymphocyte antigen (CTLA)-4, the immunosuppressive cytokine IL-10, and the tissue-homing integrin CD103. Treg cells in the retina of Gal-8-treated mice were primarily inducible Treg cells that lack the expression of neuropilin-1. In addition, Gal-8 treatment blunted production of inflammatory cytokines by retinal T helper type (TH) 1 and TH17 cells. The effect of Gal-8 on T cell differentiation and/or function was specific for tissues undergoing an active immune response, as Gal-8 treatment had no effect on T cell populations in the spleen. Given the need for rational therapies for managing human uveitis, Gal-8 emerges as an attractive therapeutic candidate not only for treating retinal autoimmune diseases, but also for other TH1- and TH17-mediated inflammatory disorders.
authors.affiliation: Program in Immunology, Sackler School of Graduate Biomedical Sciences, Tufts University, Boston, MA, United States of America.
authors.forename: James F
authors.initials: JF
authors.lastname: Sampson
authors.affiliation: Angiogenesis Laboratory, Department of Ophthalmology, Harvard Medical School, Massachusetts Eye & Ear Infirmary, Boston, MA, United States of America.
authors.forename: Eiichi
authors.initials: E
authors.lastname: Hasegawa
authors.affiliation: Angiogenesis Laboratory, Department of Ophthalmology, Harvard Medical School, Massachusetts Eye & Ear Infirmary, Boston, MA, United States of America.
authors.forename: Lama
authors.initials: L
authors.lastname: Mulki
authors.affiliation: New England Eye Center/Department of Ophthalmology, Tufts University School of Medicine, Boston, MA, United States of America.
authors.forename: Amol
authors.initials: A
authors.lastname: Suryawanshi
authors.affiliation: Laboratory for Nutrition and Vision Research, JM USDA HNRCA at Tufts University, Boston, MA, United States of America; Ophthalmology Department, People's Hospital of Inner Mongolia, Hohhot, China.
authors.forename: Shuhong
authors.initials: S
authors.lastname: Jiang
authors.affiliation: Cell, Molecular, & Developmental Biology, Sackler School of Graduate Biomedical Sciences, Tufts University, Boston, MA, United States of America.
authors.forename: Wei-Sheng
authors.initials: WS
authors.lastname: Chen
authors.affiliation: Laboratorio de Inmunopatología, Instituto de Biología y Medicina Experimental (IBYME), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), C1428 Buenos Aires, Argentina.
authors.forename: Gabriel A
authors.initials: GA
authors.lastname: Rabinovich
authors.affiliation: Angiogenesis Laboratory, Department of Ophthalmology, Harvard Medical School, Massachusetts Eye & Ear Infirmary, Boston, MA, United States of America.
authors.forename: Kip M
authors.initials: KM
authors.lastname: Connor
authors.affiliation: Program in Immunology, Sackler School of Graduate Biomedical Sciences, Tufts University, Boston, MA, United States of America; New England Eye Center/Department of Ophthalmology, Tufts University School of Medicine, Boston, MA, United States of America; Ophthalmology Department, People's Hospital of Inner Mongolia, Hohhot, China.
authors.forename: Noorjahan
authors.initials: N
authors.lastname: Panjwani
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000276:immunology; D001327:Autoimmune Diseases / Q000276:immunology*; D060908:CTLA-4 Antigen / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D004195:Disease Models, Animal; D037161:Galectins / Q000276:immunology*; D007166:Immunosuppressive Agents / Q000276:immunology; D007249:Inflammation / Q000276:immunology; D039001:Integrin alpha Chains / Q000276:immunology; D016753:Interleukin-10 / Q000276:immunology; D008198:Lymph Nodes / Q000276:immunology; D051379:Mice; D039942:Neuropilin-1 / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D058504:Th17 Cells / Q000276:immunology; D014605:Uveitis / Q000276:immunology*
chemical_list: D015703:Antigens, CD; D060908:CTLA-4 Antigen; C556707:Ctla4 protein, mouse; D037161:Galectins; D007166:Immunosuppressive Agents; D039001:Integrin alpha Chains; C091367:alpha E integrins; C526554:galectin-8, mouse; D016753:Interleukin-10; D039942:Neuropilin-1