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Monocytes with trained immunity-like signatures are associated with acute anterior uveitis in ankylosing spondylitis
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DOI：10.1002/inmd.70113.png)
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Abstract
En 中文
Acute anterior uveitis (AAU) is the most common extra-articular manifestation of ankylosing spondylitis, leading to recurrent inflammation and irreversible visual impairment. Long-term corticosteroid therapy is associated with substantial adverse effects, and effective strategies to prevent relapse are lacking. Single-cell RNA sequencing (scRNA-seq) was performed on peripheral blood mononuclear cells from seven patients with ankylosing spondylitis-acute anterior uveitis (AS-AAU) and six healthy controls, and aqueous humor samples were analyzed together with genome-wide association study (GWAS) data. Bioinformatic pipelines were used to infer cell-cell communication, metabolic programs, extracellular vesicle (EV)-related signals, and disease-relevant cell types, followed by validation in clinically derived specimens. A monocyte subcluster with upregulated cytokine and chemokine transcripts and signatures of trained immunity, termed Mono-TI, is identified. EVs potentially transport inflammatory mediators associated with Mono-TI, thereby contributing to immune dysregulation. Pseudotime analysis indicates that Mono-TI may differentiate into macrophages within the ocular microenvironment that share overlapping transcriptional features. Cell-cell interaction analysis positions Mono-TI as a highly connected node, receiving IFN-gamma signals from CD8+ T cells and natural killer (NK) cells while actively regulating neutrophils. Integrated GWAS analysis further implicates Mono-TI, together with CD8+ T cells and NK cells, as key contributors to disease pathogenesis. This study delineates the immune landscape of AS-AAU and highlights a monocyte subset with trained immunity-like transcriptional signatures and related immune cell populations as central mediators of systemic and ocular inflammation and as promising therapeutic targets.
Keywords:
ankylosing spondylitis
innate immunity
single-cell RNA sequencing
trained immunity
uveitis
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