Regenerating Gene Protein as a Novel Autoantigen in the Pathogenesis of Sjögren’s Syndrome

Abstract

Sjögren's syndrome, an autoimmune disease characterized by exocrine gland dysfunction leading to dry mouth and dry eye diseases, is typified by lymphoplasmacytic infiltrations and a progressive destruction of the salivary and lacrimal glands. Despite an ever-increasing focus on identifying the underlying etiology of Sjögren's syndrome, the factors that initiate this autoimmune disease and the mechanisms that cause the subsequent exocrine gland dysfunction remain a mystery. The original explanatory concept for the pathogenesis of Sjögren's syndrome proposed a specific, self-perpetuating, immune-mediated loss of acinar and ductal cells as the principal cause of salivary gland dysfunction. We highlight the possible involvement of regenerating gene (Reg) in the regeneration and destruction of salivary gland acinar and ductal cells in Sjögren's syndrome. The Reg gene was originally isolated as a gene specifically overexpressed in regenerating pancreatic islets and constitutes a growth factor family (Reg family). We describe how salivary gland dysfunction is initiated and maintained and how it can be regenerated or progressed, mediated by the Reg gene, Reg protein, and anti-REG autoantibodies in Sjögren's syndrome. OPEN ACCESSAntibodies 2015, 4 410

Interleukin-6/STAT pathway is responsible for the induction of gene expression of REG Iα, a new auto-antigen in Sjögren׳s syndrome patients, in salivary duct epithelial cells

“…In our previous study, we reported that REG Iα protein was overexpressed in the ductal epithelial cells of MSGs of SS patients, and that the saliva secretion was attenuated with auto-antibodies to REG Iα [22] . We also showed that mRNA levels of IL-6 and IL-8 were significantly higher in the SS MSGs than in normal MSGs [22] , [32] . In the present study we showed that REG Iα overexpression in salivary ductal cells was induced by IL-6 but not by IL-8 at the transcriptional level.…”