Differential chemokine profiles between lacrimal and salivary glands in a murine model of primary Sjögren disease

Background

Primary Sjögren disease (pSjD) is an autoimmune disorder that primarily targets the lacrimal glands (LGs) and salivary glands (SGs). However, the differences in immune pathogenesis between LGs and SGs remain poorly understood. In this study, we investigated LG-specific immune responses in comparison to SGs using a murine model of pSjD. Histopathological analyses of LGs and SGs were conducted in control and pSjD model mice.

Methods

The mRNA expression levels of 18 chemokines associated with T-cell migration were evaluated by quantitative PCR. Gene expression of selected chemokines was further examined in LG tissues by in situ hybridization. The phenotype and function of T-cells were assessed using flow cytometry and in vitro migration assays.

Results

Lymphocytic infiltration was observed earlier in LGs than in SGs in pSjD model mice. Among the chemokines analyzed, C-X-C motif chemokine ligand 4 (CXCL4) was specifically upregulated in LGs. Cxcl4 expression was localized to macrophages within LG tissues. Moreover, CXCR3 expression on CD4⁺ T-cells in lymphoid tissues was significantly higher in pSjD model mice compared to controls. T-bet was more highly expressed in CXCR3⁺CD4⁺ T cells than in CXCR3⁻CD4⁺ T cells in pSjD model mice. Finally, CXCL4 enhanced the migration of CD4⁺ T cells derived from pSjD model mice more effectively than those from control mice.

Conclusions

These findings suggest that CXCL4-producing macrophages may promote the recruitment of CXCR3⁺ Th1 cells into the LGs in pSjD, thereby contributing to LG-specific autoimmune inflammation. This mechanism may represent a potential therapeutic target for managing dry eye in pSjD.