Nature子刊：自免疫疾病抑制基因 - 生物研究-生物谷

东京大学医科学研究所人类疾病模式研究中心的岩仓洋一教授领导的研究小组通过研究中发现，人在发生关节炎时，体内一种称作“Dcir”的遗传基因有所增加，研究小组在观察该遗传基因后得出结论，这种遗传基因具有抑制自免疫性疾病发生的作用。  

在维持自然免疫中具有重要作用的“Dcir”遗传基因一旦发生变异，人就容易患上自免疫系统疾病。“Dcir”是膜蛋白的一种，存在于免疫细胞之一的树状细胞中，在树状细胞中起增殖调节等作用。研究小组在用人工去除“Dcir”遗传基因的小鼠所做的实验中观察到，随着年龄的增长，小鼠陆续开始出现自免疫相关疾病症状。这一发现对了解风湿性关节炎等疾病，以及开发新的治疗方法具有重要意义。  

该成果刊登在近期出版的美国《自然医药》杂志上。（援引科技日报）

生物谷推荐原始出处：

Nature Medicine
Published online: 20 January 2008 | doi:10.1038/nm1697

Dcir deficiency causes development of autoimmune diseases in mice due to excess expansion of dendritic cells

Noriyuki Fujikado1, Shinobu Saijo1, TomoYonezawa1,2, Kazusuke Shimamori1, Akina Ishii1, Sho Sugai1, HayatoKotaki1,4, Katsuko Sudo1,4, Masato Nose3 & Yoichiro Iwakura1

The dendritic cell immunoreceptor (official gene symbol Clec4a2,called Dcir here) is a C-type lectin receptor expressed mainly indendritic cells (DCs) that has a carbohydrate recognition domain in itsextracellular portion and an immunoreceptor tyrosine–based inhibitorymotif, which transduces negative signals into cells, in its cytoplasmicportion1. We found high Dcir expression in the joints of two mouserheumatoid arthritis models2, 3, 4. Because the structuralcharacteristics of Dcir suggest that it may have an immune regulatoryrole, and because autoimmune-related genes are mapped to the DCIR locusin humans, we generated Dcir-/- mice to learn more about thepathological roles of this molecule. We found that aged Dcir-/- micespontaneously develop sialadenitis and enthesitis associated withelevated serum autoantibodies. Dcir-/- mice showed a markedlyexacerbated response to collagen-induced arthritis. The DC populationwas expanded excessively in aged and type II collagen–immunized Dcir-/-mice. Upon treatment with granulocyte-macrophage colony–stimulatingfactor, Dcir-/- mouse–derived bone marrow cells (BMCs) differentiatedinto DCs more efficiently than did wild-type BMCs, owing to enhancedsignal transducer and activator of transcription-5 phosphorylation.These observations indicate that Dcir is a negative regulator of DCexpansion and has a crucial role in maintaining the homeostasis of theimmune system.

1. Center for Experimental Medicine, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
2. Genodive Pharma, 411 Ikehata, Isehara-shi, Kanagawa 259-1144, Japan.
3. Department of Pathology, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime 791-0295, Japan.
4. Present addresses: Genodive Pharma Inc., 411 Ikehata, Isehara-shi, Kanagawa 259-1144, Japan (H.K.); Animal Research Center, Tokyo Medical University, 6-1-1, Shinjuku, Shinjuku-ku, Tokyo 160-8402, Japan (K.S.).

Correspondence to: Yoichiro Iwakura1 e-mail: [e-mail]