Activation of innate immunity influences salivary gland function and development of Sjögren’s Syndrome (93.33)

Abstract

Abstract Sjögren’s syndrome (SS) is a chronic autoimmune disorder characterized by progressive lymphocytic infiltration within the exocrine glands. Loss of salivary gland (SG) function is a major feature of the disease. This study was undertaken to investigate the role of innate immunity activation in pathogenesis of SS. Mice were repeatedly injected with TLR3 agonist poly(I:C), and monitored for SG function and sialadenitis. Poly(I:C) treatment rapidly induced SG hypofunction. However, SG function was restored, once poly(I:C) treatment was terminated. This phenomenon was independent of the genetic background of the mice, and did not require T and B cells. Mice deficient in IFNAR1 and thereby lacking type I IFN signaling, did not loose SG function to the same extent as the wild type mice. In the autoimmune-prone NZB/W F1 mice, poly(I:C) treatment induced severe and accelerated sialadenitis. The SG in these mice showed presence of T-B cell aggregates and germinal center formation. Some of the T cells in these infiltrates were CXCR5+ICOS+ Tfh cells. Significant up-regulation in the expression of IL-21 and Il-21R genes was seen in the SG of poly(I:C) treated mice. This study demonstrates that activation of innate immunity in a genetically susceptible individual modulates the development of SS. This study also shows that type I IFN can adversely affect SG function and that IL-21 pathway and Tfh cells might be important in the pathogenesis of SS.