Inverse correlation between the number of CXCR3+ macrophages and the severity of inflammatory lesions in Sjögren's syndrome salivary glands: A pilot study

• Published in: Journal of oral pathology & medicine Vol. 47; no. 7; pp. 710 - 718
• Main Authors: Aota, Keiko, Yamanoi, Tomoko, Kani, Koichi, Nakashiro, Koh‐ichi, Ishimaru, Naozumi, Azuma, Masayuki
• Format: Journal Article
• Language: English
• Published: Denmark Wiley Subscription Services, Inc 01.08.2018
• Subjects: Aged; Antigens, CD; Antigens, Differentiation, Myelomonocytic; Autoimmunity - immunology; CD123 antigen; CD163 antigen; CD3 antigen; CD80 antigen; Chemokines; CXCL10 protein; CXCL11 protein; CXCR3; CXCR3 protein; Dendritic cells; Female; Humans; Immunofluorescence; Inflammation; Leukocyte migration; Ligands; lip salivary gland; Lymphocytes T; macrophage; Macrophages; Macrophages - immunology; Macrophages - metabolism; Macrophages - pathology; Male; Middle Aged; Pilot Projects; Receptors, Cell Surface; Receptors, CXCR3 - immunology; Receptors, CXCR3 - metabolism; Salivary gland; Salivary Glands - immunology; Salivary Glands - pathology; Severity of Illness Index; Sjogren's syndrome; Sjogren's Syndrome - immunology; Sjogren's Syndrome - pathology; Sjögren's syndrome; lip salivary gland; macrophage; Sjögren's syndrome; CXCR3
• ISSN: 0904-2512; 1600-0714; 1600-0714
• DOI: 10.1111/jop.12756

Background Mechanisms underlying immune cells’ recruitment and activation into the inflammatory lesions of lip salivary glands (LSGs) 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 CXCR3 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 CXCR3 and its ligands: CXCL9, CXCL10, and CXCL11. To identify the immune cells expressing CXCR3 in the LSGs, we performed double immunofluorescence analysis using antibodies against CD3 (pan‐T cells), CD80 (M1 macrophages), CD163 (M2 macrophages), and CD123 (plasmacytoid dendritic cells: pDCs). 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 CXCL9 and CXCL10 showed particularly intense staining in the LSG samples’ ductal cells. The CXCR3 expression was detected mainly in CD80+ and CD163+ macrophages. The number of CXCR3+CD163+ macrophages inversely correlated with the LSG inflammatory lesions’ severity (rs = −0.777, P < 0.001). Conclusions Our results suggest that the enhanced production of CXCL9 and CXCL10 from ductal cells results in the CXCR3+ macrophages’ migration. There was an inverse correlation between these two parameters: that is, the number of CXCR3+CD163+ macrophages decreased as the lymphocytic infiltration grade increased. Although CXCR3 is expressed in all of the innate immune cells, CXCR3+CD163+ M2 macrophages may contribute to the anti‐inflammatory functions in pSS lesions.