Abstract

Autoimmune uveitis mediated by T cells is a major cause of blindness in the USA and worldwide, particularly among relative young and working populations. Proposed studies will focus on the danger signals in pathogenesis of chronic autoimmune uveitis using a murine model induced by the adoptive transfer of interphotoreceptor retinoid-binding protein (IRBP)-specific T cells.
Aims described in this proposal will examine the release of danger signals initiated by uveitogenic IRBP-specific T cells, and the role of them in ocular inflammation.
Aim 1 will determine the Fas/FasL signaling in rapid release of HMGB1 from viable retinal cells after interaction with IRBP-specific T cells.
Aim 2 will examine the roleof HMGB1 in sustaining and promoting IRBP-specific T cell function during chronic intraocular inflammation. Results of these studies will further our understanding of the molecular pathogenesis of autoimmune uveitis and identify novel targets for anti-inflammatory intervention to limit visual loss.

Public Health Relevance

Autoimmune uveitis is a common ocular inflammation mediated by auto-reactive T cells. Despite a wide range of local and systemic therapies to treat this disease, uveitis is still one of the leading causes of blindness in the Western world. Experiments described in this proposal will examine danger signals in the progress of T cell immunity in the eye. The long-term goal of proposed studies is to identify targets for interventional therapy for the disease.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY024051-02
Application #
8975201
Study Section
Diseases and Pathophysiology of the Visual System Study Section (DPVS)
Program Officer
Mckie, George Ann
Project Start
2014-12-01
Project End
2018-11-30
Budget Start
2015-12-01
Budget End
2016-11-30
Support Year
2
Fiscal Year
2016
Total Cost
Indirect Cost

  Institution

Name
University of Louisville
Department
Ophthalmology
Type
Schools of Medicine
DUNS #
057588857
City
Louisville
State
KY
Country
United States
Zip Code
40208

  Publications

Yun, Juan; Xiao, Tong; Zhou, Lei et al. (2018) Local S100A8 Levels Correlate With Recurrence of Experimental Autoimmune Uveitis and Promote Pathogenic T Cell Activity. Invest Ophthalmol Vis Sci 59:1332-1342
Yun, Juan; Jiang, Guomin; Wang, Yunsong et al. (2017) The HMGB1-CXCL12 Complex Promotes Inflammatory Cell Infiltration in Uveitogenic T Cell-Induced Chronic Experimental Autoimmune Uveitis. Front Immunol 8:142
Jiang, Guomin; Wang, Yunsong; Yun, Juan et al. (2015) HMGB1 release triggered by the interaction of live retinal cells and uveitogenic T cells is Fas/FasL activation-dependent. J Neuroinflammation 12:179
Sun, Deming; Liang, Dongchun; Kaplan, Henry J et al. (2015) The role of Th17-associated cytokines in the pathogenesis of experimental autoimmune uveitis (EAU). Cytokine 74:76-80