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白细胞介素-23通过作用于一群组织驻留的起止点T细胞来引发葡萄膜炎。

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

作者信息

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

机构信息

Botnar Research Centre, and.

Sir William Dunn School of Pathology, University of Oxford, Oxford, United Kingdom.

出版信息

JCI Insight. 2025 Aug 28;10(19). doi: 10.1172/jci.insight.182616. eCollection 2025 Oct 8.

DOI:10.1172/jci.insight.182616
PMID:40875563
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12513492/
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.

摘要

复发性急性前葡萄膜炎是轴性脊柱关节炎（AxSpA）常见的关节外表现：这是一类影响脊柱、肌腱附着点、外周关节、皮肤和胃肠道的慢性炎症性疾病。AxSpA的病理学与局部组织驻留的对IL-23有反应的淋巴细胞群体有关。在这里，我们鉴定了一群由CD3+CD4-CD8-CD69+γδTCR+IL-23R+定义的眼内T细胞，它们存在于前葡萄膜中，作为小鼠眼的眼肌腱附着点类似物。局部细胞因子表达表明，葡萄膜中产生IL-23R+IL-17A的细胞对于响应IL-23引发葡萄膜炎既是必需的也是充分的。这群T细胞在人类中也存在，占据前葡萄膜腔的血管外组织。与IL-23作为AxSpA统一介质的概念一致，我们提供的证据表明，IL-23也可以在类似于肌腱附着点的眼部前房组织驻留T细胞上局部起作用，以驱动眼部炎症。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b458/12513492/f27c9da9d3e4/jciinsight-10-182616-g206.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b458/12513492/c65c452de578/jciinsight-10-182616-g201.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b458/12513492/f1b88e785350/jciinsight-10-182616-g202.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b458/12513492/6ae1f83b7f43/jciinsight-10-182616-g203.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b458/12513492/630ae9bd3362/jciinsight-10-182616-g204.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b458/12513492/71c201df7ea1/jciinsight-10-182616-g205.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b458/12513492/f27c9da9d3e4/jciinsight-10-182616-g206.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b458/12513492/c65c452de578/jciinsight-10-182616-g201.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b458/12513492/f1b88e785350/jciinsight-10-182616-g202.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b458/12513492/6ae1f83b7f43/jciinsight-10-182616-g203.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b458/12513492/630ae9bd3362/jciinsight-10-182616-g204.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b458/12513492/71c201df7ea1/jciinsight-10-182616-g205.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b458/12513492/f27c9da9d3e4/jciinsight-10-182616-g206.jpg

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