Identification of IL-18 and Th17 Cells in Salivary Glands of Patients with Sjogren's Syndrome, and Amplification of IL-17-Mediated Secretion of Inflammatory Cytokines from Salivary Gland Cells by IL-18

• Published in: The Journal of immunology (1950) Vol. 181; no. 4; p. 2898
• Main Authors: Sakai, Azusa, Sugawara, Yumiko, Kuroishi, Toshinobu, Sasano, Takashi, Sugawara, Shunji
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 15.08.2008
• Subjects: Adult; Cell Line, Tumor; Cell Movement - immunology; Cells, Cultured; Cytokines - metabolism; Humans; Inflammation Mediators - metabolism; Interleukin-17 - biosynthesis; Interleukin-17 - metabolism; Interleukin-17 - physiology; Interleukin-18 - biosynthesis; Interleukin-18 - metabolism; Interleukin-18 - physiology; Salivary Glands, Minor - immunology; Salivary Glands, Minor - metabolism; Salivary Glands, Minor - pathology; Sjogren's Syndrome - immunology; Sjogren's Syndrome - metabolism; T-Lymphocyte Subsets - immunology; T-Lymphocyte Subsets - metabolism; T-Lymphocyte Subsets - pathology
• ISSN: 0022-1767; 1550-6606; 1550-6606
• DOI: 10.4049/jimmunol.181.4.2898

IL-18 is a proinflammatory cytokine and plays an important pathogenic role in inflammatory and autoimmune disorders. IL-17 is also a proinflammatory cytokine and IL-17-secreting Th17 cells are involved in autoimmunity. However, the pathological roles of IL-18 and Th17 cells in Sjögren's syndrome (SS) remain to be elucidated. This study showed that the expression of IL-18 was detected in acinar cells, intraducts, and CD68(+) macrophages in salivary glands of SS patients, but not in those of healthy subjects or patients with chronic graft-vs-host disease, by immunohistochemistry, and immunoblot analysis revealed that 24-kDa precursor form of IL-18 (proIL-18) and 18-kDa mature IL-18 were detected in SS salivary glands. The majority of the infiltrating cells in the salivary glands of SS patients were CD4(+) T cells, and CD8(+) T cells were infiltrated to a lesser extent. The predominant expression of IL-17 was found in infiltrating CD4(+) T cells, whereas a small number of infiltrating CD8(+) T cells expressed IL-17. Human salivary gland HSY and acinar AZA3 cells constitutively expressed proIL-18 and caspase-1, and a calcium ionophore A23187 induced the secretion of IL-18 from the cells. HSY and AZA3 cells expressed IL-18R and IL-17R on the cell surface, and IL-18 amplified the secretion of IL-6 and IL-8 that were induced by low amounts of IL-17. Primary salivary gland cells from normal subjects partially confirmed these findings. These results suggest that IL-18 and Th17 cells detected in the salivary glands in SS patients are associated with the pathogenesis of SS in the salivary glands.