Tissue resident memory T cells populate the human uveal tract

作者：Andrew D. Foers, Ian R. Reekie, Lakshanie C. Wickramasinghe, Amy M. Ward, Thomas M. W. Buckley, Moustafa Attar, Soledad Aguilar-Munoa, Queen Pilapil, Maram E. A. Abdalla Elsayed, Sam Pledger, Ananya Bhalla, Robert Hedley, Sarah Hill, Dylan Windell, Keith Barton, Imran Masood, Kin Sheng Lim, Mark Christopher Coles, Jonathan P. Sherlock, Andrew D. Dick, Sarah E. Coupland, Stephen Nicholas Sansom, David A. Copland, Christopher Dominic Buckley, Srilakshmi M. Sharma, Colin J. Chu, Andrew D. Foers, Ian R. Reekie, Lakshanie C. Wickramasinghe, Amy M. Ward, Robert Hedley, Jonathan P. Sherlock, Andrew D. Dick, Sarah E. Coupland, David A. Copland, Christopher Dominic Buckley, Srilakshmi M. Sharma · 发表于：Scientific Reports · 年份：2026 · DOI：10.1038/s41598-025-33444-2 · 被引用次数：2 · 研究领域：Ocular Diseases and Behçet’s Syndrome、Ocular Oncology and Treatments、Retinal Diseases and Treatments

Abstract The current concept is that the eye is an immune privileged site endowed with innate immune regulatory networks to maintain organ function. We now have evidence that resident T cells occupy intraocular tissues. In immune-mediated inflammatory diseases, such as psoriasis and rheumatoid arthritis, tissue resident T cells trigger disease flares in the skin and joints. This suggests resident T cells in the uvea may have similar functions in non-infectious immune-mediated uveitis, a collective term for autoinflammatory and autoimmune diseases of the uveal tract causing intraocular inflammation. Here, we demonstrate by spectral cytometry and immunofluorescence imaging that non-inflamed uveal tissue contains multiple T cell subtypes including CD8 + CD103 + tissue resident memory T (T RM ) cells. Using single cell RNA & T cell receptor (TCR) sequencing to profile aqueous humour cells from donors with acute, active uveitis, we identify clonally expanded T cells which are enriched for T RM -associated genes. We further show that in donors with active uveitis, CD8 + CD103 + T cells persist within tissue in the uveal tract. Using bulk RNA sequencing and weighted gene co-expression network analysis (WGCNA) we show that quiescent iris tissue from donors with a history of uveitis are enriched for genes associated with T cell activation and antigen presentation. Finally, we demonstrate that T RM cells persist in the anterior uvea in mice following resolution of experimental autoimmu...