IL-23 drives uveitis by acting on a population of tissue-resident entheseal T cells
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.
Authors
- Stephanie G. Dakin (ORCID: https://orcid.org/0000-0003-2470-1031)
- Andrew D. Dick (ORCID: https://orcid.org/0000-0002-0742-3159)
- Sarah E. Coupland (ORCID: https://orcid.org/0000-0002-1464-2069)
- David A. Copland (ORCID: https://orcid.org/0000-0003-4044-4952)
- Serafim Kiriakidis (ORCID: https://orcid.org/0000-0003-3273-401X)
- Jonathan Sherlock (ORCID: https://orcid.org/0000-0003-2596-2209)
- Christopher Dominic Buckley (ORCID: https://orcid.org/0000-0001-6924-6402)
- Robert Hedley
- Colin J. Chu (ORCID: https://orcid.org/0000-0003-2088-8310)
- Peter C. Taylor (ORCID: https://orcid.org/0000-0001-7766-6167)
- Amy Ward (ORCID: https://orcid.org/0000-0001-8430-0999)
Institutions
- University of Liverpool (GB)
- Botho University (BW)
- University of Bristol (GB)
- University of Oxford (GB)
- Moorfields Eye Hospital (GB)
- Janssen (United States) (US)
- University College London (GB)
Publication Details
- Journal
- JCI Insight
- Published
- 2025-08-28
- DOI
- https://doi.org/10.1172/jci.insight.182616
- Citations
- 2
- Primary Topic
- Psoriasis: Treatment and Pathogenesis
- Type
- article
- Field-Weighted Citation Impact
- 1.59
Funders
- Yale University
- National Institute for Health and Care Research
- Sight Research UK
- University of Oxford
- University of Bristol
- Moorfields Eye Hospital NHS Foundation Trust
- Johnson and Johnson