日本科學(xué)技術(shù)振興機(jī)構(gòu)日前發(fā)表新聞公報(bào)說,，東京大學(xué)的科學(xué)家發(fā)現(xiàn)了調(diào)控自身免疫耐受的髓質(zhì)上皮細(xì)胞的分化和增殖機(jī)制,，這有助于人們探究自體免疫疾病的原因,，開發(fā)治療過敏和癌癥等疾病的新療法,。
正常的免疫系統(tǒng)不能耐受外界進(jìn)入的抗原,，對(duì)異己物質(zhì)發(fā)生排斥反應(yīng),，從而消除異己物質(zhì)，如攻擊并消滅入侵機(jī)體的細(xì)菌,、病毒等,。另一方面，免疫系統(tǒng)對(duì)自身的組織細(xì)胞具有耐受性,，即表現(xiàn)出無免疫應(yīng)答狀態(tài),。這種免疫耐受一旦破裂，免疫系統(tǒng)就會(huì)攻擊自身的組織細(xì)胞,，導(dǎo)致自體免疫疾病,。
新聞公報(bào)介紹說，在免疫反應(yīng)中起重要作用的T細(xì)胞產(chǎn)生于胸腺,，而且對(duì)自身臟器產(chǎn)生免疫應(yīng)答的T細(xì)胞會(huì)被機(jī)體自然除去,。如果這種自然除去的機(jī)制出現(xiàn)異常，免疫系統(tǒng)就會(huì)攻擊自身臟器,，導(dǎo)致自體免疫疾病,。近年來的研究顯示，胸腺細(xì)胞中的髓質(zhì)上皮細(xì)胞在上述自然除去機(jī)制中起著非常重要的作用,，但是髓質(zhì)上皮細(xì)胞分化,、增殖以及發(fā)揮作用的機(jī)制尚未得到充分解釋。
東京大學(xué)醫(yī)學(xué)研究所的秋山泰身等研究人員通過分析基因缺失的實(shí)驗(yàn)鼠以及進(jìn)行胸腺組織培養(yǎng)實(shí)驗(yàn),，發(fā)現(xiàn)兩種細(xì)胞表面受體——“核因子κB受體活化因子（RANK）”和“CD40”的特殊信號(hào)協(xié)調(diào)發(fā)揮作用,，使胸腺髓質(zhì)上皮細(xì)胞分化和增殖。如果誘導(dǎo)實(shí)驗(yàn)鼠髓質(zhì)上皮細(xì)胞分化和增殖的信號(hào)缺失,，那么它們體內(nèi)就會(huì)產(chǎn)生對(duì)自身臟器產(chǎn)生免疫反應(yīng)的T細(xì)胞。
公報(bào)說,，這項(xiàng)研究成果有望幫助解開至今仍有諸多謎團(tuán)的自體免疫疾病發(fā)病機(jī)制,。此外，該研究使人工控制髓質(zhì)上皮細(xì)胞的功能成為可能,，有助于開發(fā)過敏和癌癥等疾病的新療法,。
這項(xiàng)研究的相關(guān)論文已發(fā)表在最新一期美國(guó)《免疫》（Immunity）雜志的網(wǎng)絡(luò)版上。（生物谷Bioon.com）
生物谷推薦原始出處：
Immunity,，Vol 29, 423-437, 19 September 2008,，Taishin Akiyama, Jun-ichiro Inoue
The Tumor Necrosis Factor Family Receptors RANK and CD40 Cooperatively Establish the Thymic Medullary Microenvironment and Self-Tolerance
Taishin Akiyama,1,2, Yusuke Shimo,1 Hiromi Yanai,1 Junwen Qin,1 Daisuke Ohshima,1Yuya Maruyama,1 Yukiko Asaumi,1 Juli Kitazawa,1 Hiroshi Takayanagi,3 Josef M. Penninger,4Mitsuru Matsumoto,5 Takeshi Nitta,6 Yousuke Takahama,6 and Jun-ichiro Inoue1
1 Division of Cellular and Molecular biology, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokane-dai, Minato-ku, Tokyo 108-8639, Japan
2 Precursory Research for Embryonic Science and Technology, Japan Science and Technology Agency, 4-1-8 Honcho Kawaguchi, Saitama, 332-0012 Japan
3 Department of Cell Signaling, Tokyo Medical and Dental University, 1-5-45 Yushima Bunkyo-ku, Tokyo 113-8549, Japan
4 Institute of Molecular Biotechnology of the Austrian Academy Sciences, 1030 Vienna, Austria
5 Division of Molecular Immunology, Institute for Enzyme Research, University of Tokushima, 3-18-15 Kuramoto, Tokushima 770-8503, Japan
6 Division of Experimental Immunology, Institute for Genome Research, University of Tokushima, 3-18-15 Kuramoto, Tokushima 770-8503, Japan
Medullary thymic epithelial cells (mTECs) establish T cell self-tolerance through the expression of autoimmune regulator (Aire) and peripheral tissue-specific self-antigens. However, signals underlying mTEC development remain largely unclear. Here, we demonstrate crucial regulation of mTEC development by receptor activator of NF-κB (RANK) and CD40 signals. Whereas only RANK signaling was essential for mTEC development during embryogenesis, in postnatal mice, cooperation between CD40 and RANK signals was required for mTEC development to successfully establish the medullary microenvironment. Ligation of RANK or CD40 on fetal thymic stroma in vitro induced mTEC development in a tumor necrosis factor-associated factor 6 (TRAF6)-, NF-κB inducing kinase (NIK)-, and IκB kinase β (IKKβ)-dependent manner. These results show that developmental-stage-dependent cooperation between RANK and CD40 promotes mTEC development, thereby establishing self-tolerance.
