日本研究人員發(fā)現(xiàn),，兩種蛋白質(zhì)相互作用可調(diào)節(jié)抑制性Ｔ細(xì)胞的活動(dòng)，從而從分子水平上揭示了抑制性Ｔ細(xì)胞抑制免疫應(yīng)答的機(jī)制,。
根據(jù)京都大學(xué)日前發(fā)布的新聞公報(bào),，來(lái)自京都大學(xué)再生醫(yī)學(xué)研究所,、日本科學(xué)技術(shù)振興機(jī)構(gòu)和國(guó)立癌癥中心研究所的研究人員發(fā)現(xiàn)，兩種與抑制性Ｔ細(xì)胞有關(guān)的特殊蛋白質(zhì)一旦結(jié)合,，可抑制免疫反應(yīng),，它們分別是只有抑制性Ｔ細(xì)胞能夠合成的蛋白質(zhì)“Ｆｏｘｐ３”，以及對(duì)抑制性Ｔ細(xì)胞發(fā)揮功能起關(guān)鍵作用的蛋白質(zhì)——“ＡＭＬ１”,。進(jìn)一步分析顯示,，這兩種蛋白質(zhì)一旦結(jié)合，就會(huì)抑制合成白介素２的基因表達(dá),，而白介素２是放大免疫應(yīng)答的主要信息傳遞物質(zhì),。
抑制性Ｔ細(xì)胞是一種特殊的淋巴細(xì)胞，它不僅能抑制自體免疫疾病,，也會(huì)抑制針對(duì)腫瘤等的有益免疫反應(yīng),。新聞公報(bào)說(shuō)，這一研究成果為通過(guò)干擾“Ｆｏｘｐ３”和“ＡＭＬ１”的相互作用,，自由操控抑制性Ｔ細(xì)胞提供了可能性,。
研究人員指出，這一發(fā)現(xiàn)不僅有助于探究自體免疫疾病和過(guò)敏癥的發(fā)病機(jī)理,，也為開(kāi)發(fā)治療免疫疾病,、抑制臟器移植時(shí)的排異反應(yīng)、激活針對(duì)癌癥的免疫反應(yīng)等方面的新藥物打下了基礎(chǔ),。
有關(guān)研究論文發(fā)表在最新出版的英國(guó)《自然》雜志上,。
部分英文原文：
Nature advance online publication 21 March 2007 | doi:10.1038/nature05673; Received 12 December 2006; Accepted 9 February 2007; Published online 21 March 2007
Foxp3 controls regulatory T-cell function by interacting with AML1/Runx1
Masahiro Ono1,2,6, Hiroko Yaguchi3,6, Naganari Ohkura3,6, Issay Kitabayashi4, Yuko Nagamura3, Takashi Nomura1, Yoshiki Miyachi2, Toshihiko Tsukada3 and Shimon Sakaguchi1,5
Department of Experimental Pathology, Institute for Frontier Medical Sciences, and
Department of Dermatology, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan
Tumor Endocrinology Project, and,
Molecular Oncology Division, National Cancer Center Research Institute, Chuo-ku, Tokyo, 104-0045, Japan
Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency, Kawaguchi 332-0012, Japan
These authors contributed equally to this work.
Correspondence to: Shimon Sakaguchi1,5 Correspondence and requests for materials should be addressed to S.S. (Email: [email protected]).
Top of page
Naturally arising CD25+CD4+ regulatory T cells (TR cells) are engaged in the maintenance of immunological self-tolerance and immune homeostasis by suppressing aberrant or excessive immune responses, such as autoimmune disease and allergy1, 2, 3. TR cells specifically express the transcription factor Foxp3, a key regulator of TR-cell development and function. Ectopic expression of Foxp3 in conventional T cells is indeed sufficient to confer suppressive activity, repress the production of cytokines such as interleukin-2 (IL-2) and interferon-gamma (IFN-), and upregulate TR-cell-associated molecules such as CD25, cytotoxic T-lymphocyte-associated antigen-4, and glucocorticoid-induced TNF-receptor-family-related protein4, 5, 6, 7. However, the method by which Foxp3 controls these molecular events has yet to be explained. Here we show that the transcription factor AML1 (acute myeloid leukaemia 1)/Runx1 (Runt-related transcription factor 1), which is crucially required for normal haematopoiesis including thymic T-cell development8, 9, 10, 11, activates IL-2 and IFN- gene expression in conventional CD4+ T cells through binding to their respective promoters. In natural TR cells, Foxp3 interacts physically with AML1. Several lines of evidence support a model in which the interaction suppresses IL-2 and IFN- production, upregulates TR-cell-associated molecules, and exerts suppressive activity. This transcriptional control of TR-cell function by an interaction between Foxp3 and AML1 can be exploited to control physiological and pathological T-cell-mediated immune responses.
