IL-33 contributes to pathogenesis of Sjögren syndrome

Objectives: Sjögren’s syndrome (SS) is an autoimmune disease characterized by lymphocytic infiltration of the salivary and lacrimal glands with the concomitant destruction of glandular tissue. Our previous data suggested that T helper type 1 (Th1) and Th17 cytokines are essential in the induction and/or maintenance of SS, while Th2 cytokines are involved in the progression of disease process, especially local B cell activation. IL-33, recently-identified cytokine, is mainly produced by epithelial cells, vascular endothelial cells, and fibroblast. Recent studies have reported that IL-33 directly stimulates Th2 cells expressed on ST2 (IL-33 receptor) to secrete Th2 cytokines such as IL-4, IL-5, and IL-13. In this study, we thus investigated the expression and localization of IL-33 and ST2 in SS patients. 

Methods:  Biopsy specimens from the labial salivary glands (LSGs) of 15 patients with SS and 15 healthy controls were examined for (1) mRNA expression of IL-4, IL-33, and ST2; (2) expression and localization of IL-4, IL-33, and ST2 by immunohistochemical staining.

Results: mRNA expression of IL-4, IL-33, and ST2 in SS patients was significantly higher than that in controls. Moreover, mRNA expression of IL-33 in SS patients was positively correlated with both mRNA expression of IL-4 and degree of lymphocytic infiltration (focus score) in the LSGs. In immunohistochemical analysis, IL-4 and IL-33 were detected more strongly in/around ductal epithelial cells in the LSGs with strong lymphocytic infiltration. ST2 was detected in higher numbers of infiltrating lymphocytes in the LSGs with strong lymphocytic infiltration in comparison to those with weak lymphocytic infiltration. 

Conclusions:

 These results suggested that IL-33 production by ductal epithelial cells might play a key role in Th2 cytokines production and the progression of SS.