Cellular and Immunogenetic Mechanisms in Uveitis

Caspi, R.

Abstract

Cellular mechanisms in ocular immunologically mediated disease are being studied in animal models of experimental autoimmune uveoretinitis (EAU). Rats and mice are immunized with retina-derived antigens or synthetic peptides, representing fragments of these antigens, to induce EAU. Susceptibility to disease induction is being evaluated in various strains o known genetic makeup, in the hope of delineating the hereditary mechanisms that predispose to uveitis. In vivo functional long-term T-cell lines and clones are developed from lymphoid organs of rats and mice immunized with uveitogenic ocular proteins. The functional properties and antigen recepto of these cells are being studied to develop strategies for in vivo targetin of the autoimmune cells. EAU in rats and mice serves as a template for the evaluation of new drugs and compounds as well as for the study and characterization of the participating cells and their factors. The goals o these studies are to identify the immunogenetic factors predisposing to uveitic disease, learn about the pathogenic mechanisms involved, characteri the immunoreactive cells and their mediators, and finally to utilize this knowledge for designing rational approaches to immunotherapy.

Funding Agency

• Agency: National Institute of Health (NIH)
• Institute: National Eye Institute (NEI)
• Type: Intramural Research (Z01)
• Project #: 1Z01EY000184-12
• Application #: 3755550
• Support Year: 12
• Fiscal Year: 1994

Institution

• Name: U.S. National Eye Institute
• Country: United States

Publications

St Leger, Anthony J; Hansen, Anna M; Karauzum, Hatice et al. (2018) STAT-3-independent production of IL-17 by mouse innate-like ?? T cells controls ocular infection. J Exp Med 215:1079-1090

Chen, Jun; Caspi, Rachel R; Chong, Wai Po (2018) IL-20 receptor cytokines in autoimmune diseases. J Leukoc Biol 104:953-959

Kielczewski, Jennifer L; Horai, Reiko; Jittayasothorn, Yingyos et al. (2016) Tertiary Lymphoid Tissue Forms in Retinas of Mice with Spontaneous Autoimmune Uveitis and Has Consequences on Visual Function. J Immunol 196:1013-25

Lee, Ellen J; Brown, Brieanna R; Vance, Emily E et al. (2016) Mincle Activation and the Syk/Card9 Signaling Axis Are Central to the Development of Autoimmune Disease of the Eye. J Immunol 196:3148-58

Silver, Phyllis B; Silver, Phyllis; Horai, Reiko et al. (2015) Retina-specific T regulatory cells bring about resolution and maintain remission of autoimmune uveitis. J Immunol 194:3011-9

Chong, Wai Po; Horai, Reiko; Mattapallil, Mary J et al. (2014) IL-27p28 inhibits central nervous system autoimmunity by concurrently antagonizing Th1 and Th17 responses. J Autoimmun 50:12-22

London, Anat; Benhar, Inbal; Mattapallil, Mary J et al. (2013) Functional macrophage heterogeneity in a mouse model of autoimmune central nervous system pathology. J Immunol 190:3570-8

Horai, Reiko; Silver, Phyllis B; Chen, Jun et al. (2013) Breakdown of immune privilege and spontaneous autoimmunity in mice expressing a transgenic T cell receptor specific for a retinal autoantigen. J Autoimmun 44:21-33

Kyger, Madison; Worley, Aneta; Huan, Jianya et al. (2013) Effective Arrestin-Specific Immunotherapy of Experimental Autoimmune Uveitis with RTL: A Prospect for Treatment of Human Uveitis. Transl Vis Sci Technol 2:1

Hansen, Anna M; Caspi, Rachel R (2009) Targeting lymphotoxin depletes pathogenic T cells. Nat Med 15:732-3