Exacerbation of experimental autoimmune encephalomyelitis in mice deficient for DCIR, an inhibitory C-type lectin receptor
Exacerbation of experimental autoimmune encephalomyelitis in mice deficient for DCIR, an inhibitory C-type lectin receptor
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DOI：
10.1538/expanim.14-0079
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发表时间：
2015-04-01
影响因子：
2.4
通讯作者：
Iwakura, Yoichiro
中科院分区：
文献类型：
--
作者：
Seno, Akimasa;Maruhashi, Takumi;Iwakura, Yoichiro
树突状细胞免疫受体（DCIR）是一种C型凝集素受体，在其细胞外部分含有碳水化合物识别结构域，在其细胞质部分含有基于免疫受体酪氨酸的抑制基序，其将负信号转导到细胞中。以前，我们发现Dcir（-/-）小鼠由于树突状细胞（DC）的过度扩增而自发地发展自身免疫性疾病，如附着点炎和涎腺炎，这表明DCIR对于免疫系统的稳态至关重要。在这份报告中，我们分析了DCIR在实验性自身免疫性脑脊髓炎（EAE），多发性硬化症的自身免疫性疾病模型的发展中的作用。我们发现Dcir（-/-）小鼠的EAE加重，并伴有严重的脊髓脱髓鞘。Dcir（-/-）小鼠脊髓中浸润的CD 11 c（+）DC和CD 4（+）T细胞数量增加。与野生型小鼠相比，Dcir（-/-）小鼠淋巴结细胞的回忆性增殖反应更高。这些观察结果表明，DCIR是一个重要的免疫系统的负调节，和DCIR（-/-）小鼠应该是有用的分析DCIR在一系列自身免疫性疾病中的作用。
Dendritic cell immunoreceptor (DCIR) is a C-type lectin receptor containing a carbohydrate recognition domain in its extracellular portion and an immunoreceptor tyrosine-based inhibitory motif, which transduces negative signals into cells, in its cytoplasmic portion. Previously, we showed that Dcir(-/-) mice spontaneously develop autoimmune diseases such as enthesitis and sialadenitis due to excess expansion of dendritic cells (DCs), suggesting that DCIR is critically important for the homeostasis of the immune system. In this report, we analyzed the role of DCIR in the development of experimental autoimmune encephalomyelitis (EAE), an autoimmune disease model for multiple sclerosis. We found that EAE was exacerbated in Dcir(-/-) mice associated with severe demyelination of the spinal cords. The number of infiltrated CD11c(+) DCs and CD4(+) T cells into spinal cords was increased in Dcir(-/-) mice. Recall proliferative response of lymph node cells was higher in Dcir(-/-) mice compared with wild-type mice. These observations suggest that DCIR is an important negative regulator of the immune system, and Dcir(-/-) mice should be useful for analyzing the roles of DCIR in an array of autoimmune diseases.