Understanding the Development of Pathogenic CD8 T Cells in HLA-B*27-Associated Acute Anterior Uveitis (NEI R01)
Amount
Not specified
Deadline✓ Verified
Jun 30, 2031
Funder
National Eye Institute
Eligible
open to all
About This Grant
PROJECT SUMMARY (ABSTRACT) Uveitis is a potentially blinding disease that typically afflicts working-age adults. The fundamental drivers of ocular inflammation remains poorly defined, which hinders the development of new diagnostics and therapeutics. The inherited HLA-8*27 allele is associated with acute anterior uveitis, providing a well-defined population of patients to help investigate the basic mechanisms of inflammatory uveitis. Recent evidence suggests that pathogenic CDB T cells have a central role in the pathogenesis of HLA-8*27-associated acute anterior uveitis (B27AAU) through molecular mimicry. These pathogenic CD8 T cells initially recognize a bacterial peptide antigen from the intestine (YeiH), followed by cross-reactivity to self-antigens, which leads to autoimmunity. The objective of this proposal is to identify the factors that program these cross-reactive CD8 T cells to promote uveitis pathogenesis. We hypothesize that two key factors during initial activation of cross
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