AI Article Synopsis
- Sjögren disease (SjD) is an autoimmune disorder affecting salivary and tear glands; the study focused on understanding the immune cell types and their pathways involved in this condition.
- Researchers used single-cell RNA sequencing to analyze immune cell compositions in SjD mouse models, identifying key cell populations and their specific genes associated with the disease.
- Treatment with a DOCK2 inhibitor showed promising results in reducing SjD symptoms, suggesting that targeting DOCK2 could be a viable strategy for improving treatment outcomes in SjD patients.
Article Abstract
Objective: Sjögren disease (SjD) is an autoimmune condition characterized by the dysfunction of the salivary and lacrimal glands. The study aimed to decipher the pathogenic cell populations and their immunologic pathways in the salivary glands. We further determined the therapeutic effect of inhibiting dedicator of cytokinesis 2 (DOCK2) shared by novel clusters of CD8 T cells in an SjD mouse model.
Methods: This study employed single-cell RNA sequencing to examine the composition and dynamics of immune cells in the salivary glands of SjD mice. By analyzing the transcriptomic data and employing clustering analysis, a specific target was identified, leading to the treatment of mice with a targeted inhibitor.
Results: 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 showing specific genes/pathways associated with the disease. The most striking finding was the elevated expression of DOCK2 in CD8 T cells in the SjD model. This discovery is significant because subsequent treatment with a DOCK2 inhibitor 4-[3-(2-Chlorophenyl)-2-propen-1-ylidene]-1-phenyl-3,5-pyrazolidinedione (CPYPP) led to a marked amelioration of SjD signs.
Conclusion: The effectiveness of DOCK2 inhibition in alleviating SjD signs 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.
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Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11638132 | PMC |
| http://dx.doi.org/10.1002/acr2.11738 | DOI Listing |
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