Single-cell profiling reveals pathogenic role and differentiation trajectory of granzyme K+CD8+ T cells in primary Sjögren's syndrome

Basic information
Cell
26,187
Sample
12

Technology
10X Genomics
Omics
scRNA-seq
Source
PBMCs

Dataset ID
36881472
Platform
Illumina NovaSeq 6000
Species
Human
Disease
pSS,Healthy
Age range
40 - 66
Update date
2023-03-07
Summary

Primary Sjögren's syndrome (pSS) is a systemic autoimmune inflammatory disease mainly defined by T cell-dominated destruction of exocrine glands. Currently, CD8+ T cells are thought to be involved in the pathogenesis of pSS. However, the single-cell immune profiling of pSS and molecular signatures of pathogenic CD8+ T cells have not been well elucidated. Our multiomics investigation showed that both T cells and B cells, especially CD8+ T cells, were undergoing significant clonal expansion in pSS patients. TCR clonality analysis revealed that peripheral blood granzyme K+ (GZMK+) CXCR6+CD8+ T cells had higher a proportion of clones shared with CD69+CD103-CD8+ tissue-resident memory T (Trm) cells in labial glands in pSS. CD69+CD103-CD8+ Trm cells featured by high expression of GZMK were more active and cytotoxic in pSS compared with their CD103+ counterparts. Peripheral blood GZMK+CXCR6+CD8+ T cells with higher CD122 expression were increased and harbored a gene signature similar to Trm cells in pSS. Consistently, IL-15 was significantly elevated in pSS plasma and showed the capacity to promote differentiation of CD8+ T cells into GZMK+CXCR6+CD8+ T cells in a STAT5-dependent manner. In summary, we depicted the immune profile of pSS and further conducted comprehensive bioinformatics analysis and in vitro experimental investigations to characterize the pathogenic role and differentiation trajectory of CD8+ Trm cells in pSS.

Overall design

This project mainly focous on the change of CD8+ T cells in pSS patients.

Contributors

To be supplemented.

Contact

To be supplemented.

snRNA-Seq
Sample nameSample titleDiseaseGenderAgeSourceTreatmentTechnologyPlatformOmicsSample IDDataset IDAction
No data available