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

ORBIT Research Consortium; Robert Hedley; Amy Ward; Colin J Chu; Sarah E Coupland; Serafim Kiriakidis; Peter C Taylor; Stephanie G Dakin; Christopher D Buckley; Jonathan Sherlock; Andrew D Dick; David A Copland

doi:10.1172/jci.insight.182616

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

ORBIT Research Consortium, Robert Hedley, Amy Ward, Colin J Chu, Sarah E Coupland, Serafim Kiriakidis, Peter C Taylor, Stephanie G Dakin, Christopher D Buckley, Jonathan Sherlock, Andrew D Dick^*, David A Copland^*

^*Corresponding author for this work

Research output: Contribution to journal › Article (Academic Journal) › peer-review

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.

Original language	English
Article number	e182616
Number of pages	18
Journal	JCI Insight
Volume	10
Issue number	19
Early online date	28 Aug 2025
DOIs	https://doi.org/10.1172/jci.insight.182616
Publication status	Published - 8 Oct 2025

Keywords

Animals
Interleukin-23/metabolism
Mice
Humans
Interleukin-17/metabolism
Receptors, Interleukin/metabolism
Female
T-Lymphocytes/immunology
Male
Uvea/immunology
Uveitis/immunology
Disease Models, Animal
Uveitis, Anterior/immunology
Mice, Inbred C57BL

Access to Document

10.1172/jci.insight.182616Licence: CC BY

Handle.net

Persistent link

Cite this

@article{6777a24506564c34b3338b35d88fb78e,

title = "IL-23 drives uveitis by acting on a population of tissue-resident entheseal T cells",

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.",

keywords = "Animals, Interleukin-23/metabolism, Mice, Humans, Interleukin-17/metabolism, Receptors, Interleukin/metabolism, Female, T-Lymphocytes/immunology, Male, Uvea/immunology, Uveitis/immunology, Disease Models, Animal, Uveitis, Anterior/immunology, Mice, Inbred C57BL",

author = "\{ORBIT Research Consortium\} and Robert Hedley and Amy Ward and Chu, \{Colin J\} and Coupland, \{Sarah E\} and Serafim Kiriakidis and Taylor, \{Peter C\} and Dakin, \{Stephanie G\} and Buckley, \{Christopher D\} and Jonathan Sherlock and Dick, \{Andrew D\} and Copland, \{David A\}",

year = "2025",

month = oct,

day = "8",

doi = "10.1172/jci.insight.182616",

language = "English",

volume = "10",

journal = "JCI Insight",

issn = "2379-3708",

publisher = "American Society for Clinical Investigation",

number = "19",

}

TY - JOUR

T1 - IL-23 drives uveitis by acting on a population of tissue-resident entheseal T cells

AU - ORBIT Research Consortium

AU - Hedley, Robert

AU - Ward, Amy

AU - Chu, Colin J

AU - Coupland, Sarah E

AU - Kiriakidis, Serafim

AU - Taylor, Peter C

AU - Dakin, Stephanie G

AU - Buckley, Christopher D

AU - Sherlock, Jonathan

AU - Dick, Andrew D

AU - Copland, David A

PY - 2025/10/8

Y1 - 2025/10/8

N2 - 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.

AB - 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.

KW - Animals

KW - Interleukin-23/metabolism

KW - Mice

KW - Humans

KW - Interleukin-17/metabolism

KW - Receptors, Interleukin/metabolism

KW - Female

KW - T-Lymphocytes/immunology

KW - Male

KW - Uvea/immunology

KW - Uveitis/immunology

KW - Disease Models, Animal

KW - Uveitis, Anterior/immunology

KW - Mice, Inbred C57BL

U2 - 10.1172/jci.insight.182616

DO - 10.1172/jci.insight.182616

M3 - Article (Academic Journal)

C2 - 40875563

SN - 2379-3708

VL - 10

JO - JCI Insight

JF - JCI Insight

IS - 19

M1 - e182616

ER -

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

Abstract

Keywords

Access to Document

Handle.net

Fingerprint

Cite this