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

Abstract

Xiao-Xiao Yang,1,2 Chao Yang,2 Li Wang,2 Ying-Bo Zhou,2 Xiang Yuan,2 Nan Xiang,2 Yi-Ping Wang,3 Xiao-Mei Li1,2 1School of Life Sciences, University of Science and Technology of China, Hefei, Anhui, People’s Republic of China; 2The First Affiliated Hospital of USTC, Department of Rheumatology and Immunology, University of Science and Technology of China, Hefei, People’s Republic of China; 3Westmead Institute for Medical Research, University of Sydney, Sdyney, NSW, 2145, AustraliaCorrespondence: Xiao-Mei Li Email [email protected]: 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+TRM 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+TRM cells.Keywords: primary Sjogren’s syndrome, S1PR1, CD4+TRM

Keywords

• primary sjogren's syndrome
• s1pr1
• cd4+trm