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Abstract #111771 Published in IGR 24-3
Gut-licensed β7 CD4 T cells contribute to progressive retinal ganglion cell damage in glaucoma
He C; Xiu W; Chen Q; Peng K; Zhu X; Xu X; Zhang G; Fu J; Dong Q; Wu X; Li A; Liu D; Gao Y; Wang J; Wang Z; Deng B; Shuai P; Gao C; Chen Y; Yu L; Lu FScience translational medicine 2023; 15: eadg1656
Glaucoma is the leading cause of irreversible blindness. Currently, most therapeutic strategies aim to reduce elevated intraocular pressure (EIOP), but this does not always halt disease progression. Evidence suggests a role for T cells in glaucoma pathogenesis, but the underlying mechanisms remain largely unknown. Here, we found that the percentage of circulating CD4 T cells expressing a gut-homing integrin β7 was increased in patients with glaucoma and was associated with disease stage. In an EIOP-triggered glaucoma mouse model, β7 CD4 T cells infiltrated the retina in the progressive phase of glaucoma via eliciting retinal endothelial cell expression of mucosal vascular addressin cell adhesion molecule 1 (MAdCAM-1). MAdCAM-1 was minimally detected in retinas of healthy mice, and neutralization with an MAdCAM-1 antibody ameliorated retinal ganglion cell (RGC) loss and glial activity in mice with glaucoma. We furthermore found that EIOP-induced β7 CD4 T cells homed to the gut during the acute phase of glaucoma, which was essential for progressive RGC damage in diseased mice. Gut-homing β7 CD4 T cells underwent transcriptional reprogramming, showing up-regulated pathways enriched in autoimmune diseases, bacteria responses, mucosal immunity, and glial activity. Gut-homing β7 CD4 T cells gained the competence to induce retinal MAdCAM-1 expression and to cross the blood-retina barrier. Together, our study reveals a role of gut-licensed β7 CD4 T cells and MAdCAM-1 in RGC degeneration and emphasizes the importance of the "gut-retina" axis in glaucoma.
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