Pathogenic role of anti-M3 muscarinic acetylcholine receptor immune response in Sjögren's syndrome.

Abstract

M3 muscarinic acetylcholine receptor (M3R) is expressed in exocrine glands (e.g., salivary glands [SGs] and lachrymal glands), and plays a crucial role in exocrine secretion. M3R reactive T cells have been detected in circulating mononuclear cells of 40% of patients with Sjögren's syndrome (SS), and the major T cell epitopes of M3R in those patients with HLA-DR B1×0901 are located in the second loop of M3R. Moreover, autoantibodies (autoAbs) against M3R are also present in sera of around 50% of patients with SS, and several B cell epitopes, such as N-region, 1st, 2nd, and 3rd loop of M3R, have been identified. Functional analysis using human SG cell lines showed that autoAbs against the 2nd loop of M3R suppressed intracellular Ca(2+) influx, suggesting inhibition of saliva secretion. To clarify whether the M3R reactive immune response induces autoimmune sialadenitis (AIS), M3R(-/-) mice were immunized with M3R synthetic peptides and their splenocytes transferred into Rag1(-/-) mice. The recipients developed severe sialadenitis, and cell transfer studies indicated that T cells are key factors in the pathogenesis of AIS. These results indicate that the M3R immune reaction plays a key pathogenic role in AIS, suggesting that M3R molecule acts as an autoantigen in the pathogenesis of SS.

• Authors: Takayuki Sumida, Mana Iizuka, Hiromitsu Asashima, Hiroto Tsuboi, Isao Matsumoto
• Journal: Presse medicale (Paris, France : 1983) (Presse Med) Vol. 41 Issue 9 Pt 2 Pg. e461-6 (Sep 2012) ISSN: 2213-0276 [Electronic] France
• PMID: 22884125 (Publication Type: Journal Article)
• Copyright: Copyright © 2012 Elsevier Masson SAS. All rights reserved.

Chemical References

• Autoantibodies
• Autoantigens
• Calcium Channels
• Epitopes, B-Lymphocyte
• Epitopes, T-Lymphocyte
• HLA-DRB1 Chains
• Homeodomain Proteins
• Interleukin-17
• Receptor, Muscarinic M3
• RAG-1 protein
• Interferon-gamma

Topics

• Amino Acid Motifs (immunology)
• Animals
• Autoantibodies (immunology)
• Autoantigens (immunology)
• Autoimmune Diseases (immunology)
• CD4-Positive T-Lymphocytes (immunology)
• Calcium Channels (immunology)
• Calcium Signaling (immunology)
• Cell Line
• Cell Transplantation
• Epitopes, B-Lymphocyte (immunology)
• Epitopes, T-Lymphocyte (immunology)
• Genes, RAG-1 (immunology)
• HLA-DRB1 Chains (immunology)
• Homeodomain Proteins (genetics, immunology)
• Humans
• Interferon-gamma (immunology)
• Interleukin-17 (immunology)
• Mice
• Mice, Knockout
• Receptor, Muscarinic M3 (immunology)
• Saliva (metabolism)
• Sialadenitis (immunology)
• Sjogren's Syndrome (immunology)
• Spleen (cytology, immunology)