Pathogenic role of immune response to M3 muscarinic acetylcholine receptor in Sjögren's syndrome-like sialoadenitis.
The aim of this study was to clarify the role of the immune response to muscarinic type 3 receptor (M3R) in the pathogenesis of Sjögren's syndrome (SS). M3R(-/-) mice were immunized with murine M3R peptides and their splenocytes were inoculated into Rag1(-/-) (M3R(-/-)→Rag1(-/-)) mice. M3R(-/-)→Rag1(-/-) mice had high serum levels of anti-M3R antibodies and low saliva volume. Histological examination showed marked infiltration of mononuclear cells in the salivary glands and immunohistochemistry demonstrated that the majority of these cells were CD4(+) T cells with a few B cells and several IFN-γ- and IL-17-producing cells. Apoptotic cells were present in the salivary glands of M3R(-/-)→Rag1(-/-) mice. Moreover, transfer of only CD3(+) T cells from M3R(-/-) immunized with M3R peptides into Rag1(-/-) mice resulted in cell infiltration and destruction of epithelial cells in the salivary glands, suggesting that M3R reactive CD3(+) T cells play a pathogenic role in the development of autoimmune sialoadenitis. Our findings support the notion that the immune response to M3R plays a crucial role in the pathogenesis of SS-like autoimmune sialoadenitis.
Iizuka
Mana
M
Division of Clinical Immunology, Doctoral Programs in Clinical Sciences, Graduate School Comprehensive Human Science, University of Tsukuba, 1-1-1 Tenodai, Tsukuba City, Ibaraki 305-8575, Japan.
Wakamatsu
Ei
E
Tsuboi
Hiroto
H
Nakamura
Yumi
Y
Hayashi
Taichi
T
Matsui
Minoru
M
Goto
Daisuke
D
Ito
Satoshi
S
Matsumoto
Isao
I
Sumida
Takayuki
T
D019264:Adoptive Transfer; D000818:Animals; D017209:Apoptosis; D001323:Autoantibodies / Q000097:blood; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000276:immunology / Q000473:pathology; D006801:Humans; D007114:Immunization; D007371:Interferon-gamma / Q000378:metabolism; D020381:Interleukin-17 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010446:Peptide Fragments / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D043587:Receptor, Muscarinic M3 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D012469:Salivary Glands / Q000473:pathology; D012793:Sialadenitis / Q000097:blood / Q000276:immunology*; D012859:Sjogren's Syndrome / Q000276:immunology*
D001323:Autoantibodies; D020381:Interleukin-17; D010446:Peptide Fragments; D043587:Receptor, Muscarinic M3; D007371:Interferon-gamma