Objective: Although extensive research has been carried out on CD4⁺T cells infiltrating the labial glands in patients with primary Sjögren’s Syndrome (pSS), it is still unclear how CD4⁺T cells remain in the labial gland tissue and develop into tissue resident cells. The aim of this study was to investigate the molecular mechanism by which CD4⁺T reside in labial glandular tissue of pSS patients.
Methods: Lymphocyte infiltration in labial salivary glands (LSG) of pSS patients was detected by H&E staining. Expression of sphingosine-1-phosphate receptor 1 (S1PR1) in LSG was examined by Immunohistochemistry. Immunofluorescence analyses were utilized to detect the co-expression of CD4, CD69 and S1PR1 in T cells of LSG of pSS patients. Expression of gene S1pr1  in peripheral blood CD4⁺T cells of healthy controls and pSS patients was detected by quantitative real-time PCR (QPCR). QPCR was used to examine the expression of gene S1pr1, Klf2, and Cd69  in the CD4⁺T cells that were co-cultured in vitro with cytokines TNF-α, TGF-β, and IL-33.
Results: S1PR1 was expressed in the infiltrating monocytes in LSG of pSS patients, and S1PR1 was weakly or even not expressed in cytoplasm of CD4⁺CD69⁺T_RM cells of LSG in patients with pSS. Expression of gene S1pr1  in peripheral blood CD4⁺T cells of pSS patients was about three-fifths of that of healthy controls (P < 0.05). Expression of genes S1pr1  (P < 0.001) and Klf-2  (P < 0.001) was significantly decreased, and the expression of gene Cd69  (P < 0.05) was significantly increased in peripheral blood CD4⁺T cells of pSS patients co-cultured in vitro with cytokines TNF-α, TGF-β, and IL-33.
Conclusion: Our study suggests that the decrease of S1pr1  gene expression may provide a molecular basis for promoting the tissue retention and development of CD4⁺CD69⁺T_RM cells.
Keywords: primary Sjogren’s syndrome, S1PR1, CD4⁺T_RM