GZMK+CD8+ T cells Target a Specific Acinar Cell Type in Sjögren's Disease.
Blake M WarnerThomas PranzatelliPaola PerezAnson KuBruno Fernandes MatuckKhoa HuynhShunsuke SakaiMehdi AbedShyh-Ing JangEiko YamadaKalie DominickZara AhmedAmanda J OliverRachael WasikowskiQuinn T EasterM Teresa MagoneAlan BaerEileen PelayoZohreh KhavandgarSarthak GuptaDavid KleinerChristopher J LessardAmy Darise FarrisDaniel MartinRobert J MorellChangyu ZhengNicholas RachmaninoffJose Maldonado-OrtizXufeng QuMarit AureMohammad DezfulianRoss LakeSarah A TeichmannDaniel BarberLam TsoiAdam G SowalskyKatarzyna TycJohann E GudjonssonKevin ByrdPhilip JohnsonJinze LiuJohn ChioriniPublished in: Research square (2023)
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
- immune response
- rna seq
- induced apoptosis
- cell therapy
- public health
- healthcare
- end stage renal disease
- stem cells
- chronic kidney disease
- high throughput
- rheumatoid arthritis
- prognostic factors
- toll like receptor
- newly diagnosed
- disease activity
- climate change
- systemic lupus erythematosus
- cell proliferation
- health information
- risk assessment
- drug delivery
- human health
- health promotion
- pluripotent stem cells