Autoantibodies against muscarinic acetylcholine receptor M₃ in Sjogren’s syndrome and corresponding mouse models

Muscarinic acetylcholine receptor M₃ (M3R) is a GPCR on exocrine gland cells involved in fluid secretion. In the last two decades, evidence has been accumulated arguing for a role of autoantibodies (aab) against M3R in the development of Sjögren’s syndrome (SS). In this review, we provide an updated overview on this issue and critically discuss the relation between autoimmunity to M3R and SS pathogenesis. Clinical data as well as findings from experimental disease were summarized in categories addressing the presence of aab against M3R in SS patients, the function of anti-M3R aab, the association of aab against M3R with SS-related phenotypes, in vivo pathogenicity of transferred aab against M3R in mice, and mouse models induced via immunization with M3R. Based on these comprehensive data, we propose a hypothetic model for the role of aab against M3R in the pathogenesis of SS.