IL-23 drives uveitis by acting on a population of tissue-resident entheseal T cells.

Hedley, Robert; Ward, Amy; Chu, Colin J; Coupland, Sarah E; Kiriakidis, Serafim; Taylor, Peter C; Dakin, Stephanie G; ORBIT Research Consortium et al. · JCI Insight · 2025

basic_science · Level V

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Abstract

Recurrent acute anterior uveitis is a frequent extra-articular manifestation of the axial spondyloarthropathies (AxSpA): chronic inflammatory diseases affecting the spine, enthesis, peripheral joints, skin, and gastrointestinal tract. Pathology in AxSpA has been associated with local tissue-resident populations of IL-23 responsive lymphoid cells. Here we characterize a population of ocular T cell defined by CD3+CD4-CD8-CD69+γδTCR+IL-23R+ that reside within the anterior uvea as an ocular entheseal analogue of the mouse eye. Localized cytokine expression demonstrates that uveal IL-23R+ IL-17A-producing cells are both necessary and sufficient to drive uveitis in response to IL-23. This T cell population is also present in humans, occupying extravascular tissues of the anterior uveal compartment. Consistent with the concept of IL-23 as a unifying mediator in AxSpA, we present evidence that IL-23 can also act locally on tissue resident T cells in the anterior compartment of the eye at sites analogous to the enthesis to drive ocular inflammation.

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