Role of immune response to M3 muscarinic acethylcholine receptor in the pathogenesis of Sjögren's syndrome.

Sjögren's syndrome (SS) is a chronic autoimmune disease characterized by lymphocytic infiltration of salivary glands, in which CD4(+) T cells are predominant. These infiltrating T cells play a crucial role in the generation of SS. Previous studies showed that autoantibodies and auto-reactive T cells against M3 muscarinic acethylcholine receptor (M3R) were detected in patients with SS. In this study, to reveal the pathological mechanisms underlying immune response against M3R, we tried to induce SS like sialoadenitis. M3R knockout (M3R(-/-)) mice were immunized with murine M3R peptides. Their splenocytes were isolated and transferred into Rag1 knockout (Rag1(-/-)) mice. Mononuclear cells infiltration was detected in salivary glands of Rag1(-/-) mice inoculated splenocytes of M3R(-/-) mice immunized with M3R peptides. Moreover we transferred CD3(+) cells from splenocytes of M3R(-/-) mice immunized with M3R peptides into Rag1(-/-) mice. In their salivary glands, mononuclear infiltration was also detected. These findings suggest that the immune response to M3R plays a crucial role in the generation of SS like sialoadenitis.