Abstract
The second extracellular loop (LFWQYFVGKRTVPPGECFIQFLSEPTITFGTAI, aa 205–237) of muscarinic acetylcholine 3 receptor (M3R) has been reported to be an epitope for autoantibodies generated during certain autoimmune disorders, including Sjögren's syndrome (SS). Autoantibodies against M3R228–237 have been shown to interfere with the function of M3R. However, few studies have been performed on the M3R205–227 peptide of the second extracellular loop. In the current study, we sought to investigate the effect of M3R208–227 peptide immunization on autoimmune response in NOD/LtJ mice. We synthesized the M3R208–227 peptide and immunized NOD/LtJ mice to investigate whether peptide-specific antibodies could be generated and whether immunization would lead to changes in autoimmune response in NOD/LtJ mice. Our results demonstrate that the secretions of Th-1, Th-2, and Th-17 cytokines are downregulated and lymphocytic infiltration is improved in the salivary glands and lacrimal glands following immunization with M3R208–227 peptide in NOD/LtJ mice, suggesting that peptide immunotherapy using the M3R208–227 peptide may represent a potential therapeutic alternative.
Highlights
The muscarinic acetylcholine 3 receptor (M3R) plays a key role in mediating exocrine protein secretion in the salivary and lacrimal glands
Autoimmune responses against M3Rs contribute to the development of sicca symptoms and autonomic dysfunction in patients with both primary and secondary Sjogren’s syndrome (SS) [1, 2], which suggests that disorders related to M3R signaling in the salivary and lacrimal glands can lead to reduced secretions from these glands
Mice (Figures 1(a), 1(b), and 1(c)). These results showed that peptide-specific antibodies were successfully and generated only in animals immunized with the M3R208−227 peptide
Summary
The muscarinic acetylcholine 3 receptor (M3R) plays a key role in mediating exocrine protein secretion in the salivary and lacrimal glands. Autoimmune responses against M3Rs contribute to the development of sicca symptoms and autonomic dysfunction in patients with both primary and secondary Sjogren’s syndrome (SS) [1, 2], which suggests that disorders related to M3R signaling in the salivary and lacrimal glands can lead to reduced secretions from these glands. The second extracellular loop (LFWQYFVGKRTVPPGECFIQFLSEPTITFGTAI, aa 205–237) of M3R has been reported to be an epitope for autoantibodies generated during certain autoimmune disorders [4,5,6,7], and autoantibodies against M3R205−237 have been shown to interfere with the function of. The study by Naito et al [13] demonstrated that VPPGECFKQFLSEPT (M3R 223I → K) and VPPGECFIAFLSEPT (M3R 224Q → A) for the anchor positions binding to HLA-DR B1∗0901 were candidate altered peptide ligands of the second extracellular domain of M3R
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