Identification of IL-18 and Th17 cells in salivary glands of patients with Sjögren's syndrome, and amplification of IL-17-mediated secretion of inflammatory cytokines from salivary gland cells by IL-18.
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.
Sakai
Azusa
A
Division of Oral Immunology, Department of Oral Biology, Tohoku University Graduate School of Dentistry, Sendai, Japan.
Sugawara
Yumiko
Y
Kuroishi
Toshinobu
T
Sasano
Takashi
T
Sugawara
Shunji
S
D000328:Adult; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism*; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism*; D020381:Interleukin-17 / Q000096:biosynthesis* / Q000378:metabolism / Q000502:physiology; D020382:Interleukin-18 / Q000096:biosynthesis* / Q000378:metabolism / Q000502:physiology; D012470:Salivary Glands, Minor / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D012859:Sjogren's Syndrome / Q000276:immunology* / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism / Q000473:pathology
D016207:Cytokines; D018836:Inflammation Mediators; D020381:Interleukin-17; D020382:Interleukin-18