東京大學(xué)醫(yī)科學(xué)研究所人類疾病模式研究中心的巖倉洋一教授領(lǐng)導(dǎo)的研究小組通過研究中發(fā)現(xiàn),，人在發(fā)生關(guān)節(jié)炎時，體內(nèi)一種稱作“Dcir”的遺傳基因有所增加,，研究小組在觀察該遺傳基因后得出結(jié)論，這種遺傳基因具有抑制自免疫性疾病發(fā)生的作用,。
在維持自然免疫中具有重要作用的“Dcir”遺傳基因一旦發(fā)生變異,，人就容易患上自免疫系統(tǒng)疾病,。“Dcir”是膜蛋白的一種,，存在于免疫細(xì)胞之一的樹狀細(xì)胞中，在樹狀細(xì)胞中起增殖調(diào)節(jié)等作用,。研究小組在用人工去除“Dcir”遺傳基因的小鼠所做的實(shí)驗(yàn)中觀察到,，隨著年齡的增長，小鼠陸續(xù)開始出現(xiàn)自免疫相關(guān)疾病癥狀,。這一發(fā)現(xiàn)對了解風(fēng)濕性關(guān)節(jié)炎等疾病,，以及開發(fā)新的治療方法具有重要意義。
該成果刊登在近期出版的美國《自然醫(yī)藥》雜志上,。（援引科技日報(bào)）
生物谷推薦原始出處：
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, Tomo Yonezawa1,2, Kazusuke Shimamori1, Akina Ishii1, Sho Sugai1, Hayato Kotaki1,4, 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 in dendritic cells (DCs) that has a carbohydrate recognition domain in its extracellular portion and an immunoreceptor tyrosine–based inhibitory motif, which transduces negative signals into cells, in its cytoplasmic portion1. We found high Dcir expression in the joints of two mouse rheumatoid arthritis models2, 3, 4. Because the structural characteristics of Dcir suggest that it may have an immune regulatory role, and because autoimmune-related genes are mapped to the DCIR locus in humans, we generated Dcir-/- mice to learn more about the pathological roles of this molecule. We found that aged Dcir-/- mice spontaneously develop sialadenitis and enthesitis associated with elevated serum autoantibodies. Dcir-/- mice showed a markedly exacerbated response to collagen-induced arthritis. The DC population was expanded excessively in aged and type II collagen–immunized Dcir-/- mice. Upon treatment with granulocyte-macrophage colony–stimulating factor, Dcir-/- mouse–derived bone marrow cells (BMCs) differentiated into DCs more efficiently than did wild-type BMCs, owing to enhanced signal transducer and activator of transcription-5 phosphorylation. These observations indicate that Dcir is a negative regulator of DC expansion and has a crucial role in maintaining the homeostasis of the immune system.
Center for Experimental Medicine, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
Genodive Pharma, 411 Ikehata, Isehara-shi, Kanagawa 259-1144, Japan.
Department of Pathology, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime 791-0295, Japan.
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: [email protected]
