GZMK+CD8+ T cells Target A Specific Acinar Cell Type in Sjögren's Disease.
Thomas J F PranzatelliPaola PerezAnson T KuBruno Fernandes MatuckKhoa HuynhDaniel L BarberMehdi AbedShyh-Ing JangEiko YamadaKalie DominickZara AhmedAmanda J OliverRachael WasikowskiQuinn T EasterAlan N BaerEileen PelayoZohreh KhavandgarDavid E KleinerM Teresa MagoneSarthak GuptaChristopher J LessardAmy Darise FarrisPeter Denis BurbeloDaniel MartinRobert J MorellChangyu ZhengNicholas RachmaninoffJose O MaldonadoXufeng QuMarit H AureMohammad H DezfulianRoss LakeSarah A TeichmannDaniel L BarberLam C TsoiAdam G SowalskyKatarzyna M TycJinze LiuJohann E GudjonssonKevin M ByrdPhilip L F JohnsonJohn A ChioriniBlake M WarnerPublished in: Research square (2024)
Sjögren's Disease (SjD) is a systemic autoimmune disease without a clear etiology or effective therapy. Utilizing unbiased single-cell and spatial transcriptomics to analyze human minor salivary glands in health and disease we developed a comprehensive understanding of the cellular landscape of healthy salivary glands and how that landscape changes in SjD patients. We identified novel seromucous acinar cell types and identified a population of PRR4+CST3+WFDC2 - seromucous acinar cells that are particularly targeted in SjD. Notably, GZMK +CD8 T cells, enriched in SjD, exhibited a cytotoxic phenotype and were physically associated with immune-engaged epithelial cells in disease. These findings shed light on the immune response's impact on transitioning acinar cells with high levels of secretion and explain the loss of this specific cell population in SjD. This study explores the complex interplay of varied cell types in the salivary glands and their role in the pathology of Sjögren's Disease.
Keyphrases
- single cell
- rna seq
- immune response
- healthcare
- cell therapy
- end stage renal disease
- endothelial cells
- mental health
- newly diagnosed
- cell cycle arrest
- chronic kidney disease
- ejection fraction
- drug delivery
- inflammatory response
- cell death
- prognostic factors
- mesenchymal stem cells
- signaling pathway
- cancer therapy
- cell proliferation
- health information
- anti inflammatory