Molecular Mechanism of Sphingosine-1-Phosphate Receptor 1 Regulating CD4 Tissue Memory in situ T Cells in Primary Sjogren's Syndrome.

Objective: Although extensive research has been carried out on CD4T cells infiltrating the labial glands in patients with primary Sjögren's Syndrome (pSS), it is still unclear how CD4T 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 CD4T 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 in peripheral blood CD4T cells of healthy controls and pSS patients was detected by quantitative real-time PCR (QPCR). QPCR was used to examine the expression of gene and in the CD4T 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 CD4CD69T cells of LSG in patients with pSS. Expression of gene in peripheral blood CD4T cells of pSS patients was about three-fifths of that of healthy controls (P < 0.05). Expression of genes (P < 0.001) and (P < 0.001) was significantly decreased, and the expression of gene (P < 0.05) was significantly increased in peripheral blood CD4T 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 gene expression may provide a molecular basis for promoting the tissue retention and development of CD4CD69T cells.