Single-cell transcriptomic profiling reveals functional heterogeneity and regulatory programs of neutrophils in experimental autoimmune uveitis.
Most retinal neutrophils in autoimmune uveitis mice show a pro-inflammatory activation state
Single-cell transcriptomic profiling reveals functional heterogeneity and regulatory programs of neutrophils in experimental autoimmune uveitis.
Autoimmune uveitis (autoimmune uveitis) is a vision-threatening ocular autoimmune disease.
This study employed single-cell RNA sequencing (scRNA-seq) to systematically characterize neutrophils in the retina of experimental autoimmune uveitis (experimental autoimmune uveitis) mice and to elucidate their regulatory mechanisms. scRNA-seq data were obtained from the mouse retinal samples of experimental autoimmune uveitis and subjected to preprocessing, cell type annotation, neutrophil activation states analysis, differential gene expression analysis, functional enrichment, and transcription factor network inference, enabling a comprehensive exploration of neutrophil heterogeneity and functional features.
over three-quarters of retinal neutrophils were locked in an inflammation-driving state
Experimental autoimmune uveitis retinas exhibited markedly enhanced immune cell infiltration, with a significant increase in neutrophil proportion.
Functional modules displayed a coordinated regulatory pattern.
Transcription factor network analysis identified upregulated factors such as Jun and downregulated factors such as Stat6, indicating their respective regulatory roles in pro-inflammatory and anti-inflammatory activation states.
Several downstream target genes, including Arpp19 and Lyrm2, were co-regulated by multiple transcription factors.
This study reveals the heterogeneous features and regulatory networks of retinal neutrophils in experimental autoimmune uveitis mice, clarifies differences between these neutrophil activation states, and identifies key regulatory molecules.
These findings provide a theoretical foundation for understanding the pathogenesis of uveitis and for the development of precise therapeutic targets.