Pathogenic role of immune response to M3 muscarinic acetylcholine receptor in Sjogren's syndrome-like sialoadenitis
Pathogenic role of immune response to M3 muscarinic acetylcholine receptor in Sjogren's syndrome-like sialoadenitis
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DOI：
10.1016/j.jaut.2010.08.004
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发表时间：
2010-12-01
影响因子：
12.8
通讯作者：
Sumida, Takayuki
中科院分区：
文献类型：
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作者：
Iizuka, Mana;Wakamatsu, Ei;Sumida, Takayuki
为探讨M3R免疫应答在干燥S综合征(SS)发病机制中的作用，用小鼠M3R多肽免疫小鼠，并将其脾细胞接种于Rag1(-/-)(M3R(-/-)->；Rag1(-/-))小鼠，观察M3R(-/-)-GT；Rag1(-/-)小鼠血清抗M3R抗体水平高，唾液量低，组织学检查显示唾液腺内有明显的单核细胞浸润，免疫组织化学显示这些细胞以CD4(+)T细胞为主，少数为B细胞，少数产生干扰素-γ和IL-17细胞；此外，将M3R多肽免疫的M3R(-/-)小鼠的CD3(+)T细胞转移到Rag1(-/-)小鼠体内，可导致涎腺上皮细胞的浸润和破坏，提示M3R反应性CD3(+)T细胞在自身免疫性涎腺炎的发生发展中起致病作用。我们的发现支持对M3R的免疫应答在SS样自身免疫性涎腺炎的发病机制中起关键作用的观点。(C)2010 Elsevier Ltd版权所有
The aim of this study was to clarify the role of the immune response to muscarinic type 3 receptor (M3R) in the pathogenesis of Sjogren 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-gamma- 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 (c) 2010 Elsevier Ltd All rights reserved