Inverse correlation between the number of<scp>CXCR</scp>3⁺macrophages and the severity of inflammatory lesions in Sjögren's syndrome salivary glands: A pilot study

Abstract

Background Mechanisms underlying immune cells’ recruitment and activation into the inflammatory lesions of lip salivary glands ( LSG s) from primary Sjögren's syndrome ( pSS ) patients are incompletely understood. Chemokines play pivotal roles in these processes, so we investigated the clinical significance of chemokine receptor CXCR 3 and its ligands in the autoimmune lesions of pSS . Methods We histologically determined the grade of LSG samples from 22 patients with pSS and subjected the samples to immunofluorescence analysis to determine the expressions of CXCR 3 and its ligands: CXCL 9, CXCL 10, and CXCL 11. To identify the immune cells expressing CXCR 3 in the LSG s, we performed double immunofluorescence analysis using antibodies against CD 3 (pan‐T cells), CD 80 (M1 macrophages), CD 163 (M2 macrophages), and CD 123 (plasmacytoid dendritic cells: pDC s). The relationship between the grade of lymphocytic infiltration and the number of positively stained cells was analyzed by Spearman's rank correlation test. Results The expressions of CXCL 9 and CXCL 10 showed particularly intense staining in the LSG samples’ ductal cells. The CXCR 3 expression was detected mainly in CD 80 + and CD 163 + macrophages. The number of CXCR 3 + CD 163 + macrophages inversely correlated with the LSG inflammatory lesions’ severity ( r s = −0.777, P &lt; 0.001). Conclusions Our results suggest that the enhanced production of CXCL 9 and CXCL 10 from ductal cells results in the CXCR 3 + macrophages’ migration. There was an inverse correlation between these two parameters: that is, the number of CXCR 3 + CD 163 + macrophages decreased as the lymphocytic infiltration grade increased. Although CXCR 3 is expressed in all of the innate immune cells, CXCR 3 + CD 163 + M2 macrophages may contribute to the anti‐inflammatory functions in pSS lesions.