Single-cell transcriptomics reveals a pivotal role of DOCK2 in Sjögren’s disease

Abstract

Sjögren's disease (SjD) is an autoimmune condition characterized by the dysfunction of the salivary and lacrimal glands. This study utilized single-cell RNA sequencing to analyze the immune cell composition and dynamics within the salivary glands of SjD mice. The results showed diverse immune cell types, including B cells, CD4+ T cells, CD8+ T cells, macrophages, and natural killer cells. We identified specific clusters possessing phenotypic characteristics of immune cell subpopulations, thereby uncovering the gene/pathway function. The most striking finding was the elevated expression of DOCK2 in CD8+ T cells in the SjD model. This discovery is significant, as subsequent treatment with a DOCK2 inhibitor led to a marked amelioration of symptoms associated with SjD. The effectiveness of DOCK2 inhibition in alleviating symptoms highlights the potential of DOCK2 as a therapeutic target, opening new avenues for treatment strategies that could modulate the immune response more effectively in SjD.