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Guomin Jiang, Yunsong Wang, Yuan Zhao, Amir Reza Hajrasouliha, Jinhui Wu, Deming Sun, Henry J Kaplan, Hui Shao; CXCL 12 is a chemoattract induced by HMGB1 in T cell induced uveitis (tEAU). Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):876.
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In EAU induced by injection of uveitogenic, interphotoreceptor retinoid-binding protein (IRBP)-specific T cells (tEAU) in mice, we have previously reported that high mobility group box 1 (HMGB1), an important endogenous danger signal, was an early and critical mediator for induction of disease. Our current study explores the role of HMGB1 in intraocular inflammation, focusing on its role in recruiting infiltrating cells into the eye.
Supernatants collected from the co-culture of retinal explants with HMGB1 or IRBP-specific T cells in the presence or absence of anti-HMGB1 Ab were tested for their chemoattractive effect on leukocytes. Mice receiving IRBP-specific T cells were treated with CXCR4 antagonist (AMD3100), and intraocular inflammation was examined by funduscopy and histology.
HMGB1 alone or culture supernatants from retinal explants did not attract leukocytes. However, supernatants from retinal explants treated with HMGB1 or co-cultured with IRBP-specific T cells did attract lymphocytes; co-culture in the presence of anti-HMGB1 Ab abrogated chemoattraction, implying molecules released by HMGB1 treated retinal cells are chemoattractive. Moreover, supernatants neutralized by anti-CXCL12 Ab or leukocytes pre-treated with AMD3100 (an antagonist of CXCR4, a receptor for CXCL12) resulted in decreased chemoattraction. Finally, tEAU was significantly inhibited by AMD3100.
CXCL12, a ligand for CXCR4, is produced by retinal cells after exposure to HMGB1 and is a chemoattract for lymphocytes in tEAU.
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