Abstract 1083: New Murine Model for Sjogren's Syndrome Established by M3 Muscarinic Acetylcholine Receptor Immunization
Thomas Grader-Beck
Authors
Ei Wakamatsu, Yumi Nakamura, Isao Matsumoto, Hiroto Tsuboi, Daisuke Goto, Satoshi Ito, Akito Tsutsumi, Takayuki Sumida.
Background
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. Previously studies showed that autoantibody and auto-reactive T cells against M3 muscarinic acetylcholine receptor (M3R) were detected in SS patients. In this study, to establish the new murine model for SS, we immunized M3R to naïve mice and analyzed immune response to M3R.
Methods
C57BL/6 mice were immunized intradermally with 200ug recombinant human M3R protein in adjuvans. 1) Salivary glands were examined histologically by H&E staining on day 14 for cell infiltrates and Immunoglobulin deposition. Anti-M3R antibodies (Abs) from immunized mice were measured by ELISA.
Results
1) In the salivary glands of M3R immunized C57BL/6 mice on day 14, infiltration of lymphocytes were identified, whereas no infiltration was detected in control mice. 2) Immunohistochemical study demonstrated that infiltrating lymphocytes were Thy1+ T cells, but not B cells. 3) Although anti-M3R Abs were specifically detected in M3R immunized mice by ELISA, the deposition of IgG to salivary glands was not detected.
Conclusions
In the present study, we clarified that infiltration of T cells was detected in the salivary gland with M3R immunized mice. These findings suggest the possibility that autoimmune response against M3R plays a crucial role in the generation of sialoadenitis in patients with SS, and this mouse will be useful for a new model for Sjögren's syndrome.
Editorial Comment:
Antibodies to muscarinic acetylcholine receptor (M3R) in human Sjogren’s disease and mouse models of Sjogren’s syndrome have been described previously by several groups. M3R expression has been found to be upregulated on acinar cells in salivary glands of Sjogren’s patients and M3R antibodies reversibly inhibit mechanisms of fluid secretion. This study by Wakamatsu et al. Introduces a potentially powerful new mouse model to study the role of M3R antibodies for pathogenesis of the disease. Induction is straightforward by immunization with recombinant immunogen. Inducibility on the C57B6 background makes it easy to introduce specific gene deficient mice. Further characterization of the model is needed, in particular whether salivary flow is indeed inhibited in the presence of disease. Passive transfer experiments using serum from disease mice would also be a desirable confirmation of principle.
