日本理化研究所近日發(fā)表新聞公報(bào)說,，其研究人員與美國同行經(jīng)動物實(shí)驗(yàn)發(fā)現(xiàn)，負(fù)責(zé)合成轉(zhuǎn)錄因子Mina的基因存在單核苷酸多態(tài)性,，這一特點(diǎn)與過敏癥發(fā)病相關(guān)。
有的人容易過敏,，有的人則不易過敏,，醫(yī)學(xué)界普遍認(rèn)為過敏體質(zhì)與遺傳有關(guān)，但迄今尚未完全了解導(dǎo)致過敏體質(zhì)的基因和具體機(jī)制,。
新聞公報(bào)說,，理化研究所免疫、過敏科學(xué)綜合研究中心的研究人員與美國田納西州一所兒童疾病研究機(jī)構(gòu)的同行,，對比了屬于過敏體質(zhì)的實(shí)驗(yàn)鼠和不易過敏的實(shí)驗(yàn)鼠,，發(fā)現(xiàn)它們體內(nèi)負(fù)責(zé)指導(dǎo)合成轉(zhuǎn)錄因子Mina的基因存在多處單核苷酸多態(tài)性。其結(jié)果,，不易過敏的實(shí)驗(yàn)鼠體內(nèi)T細(xì)胞中存在大量Mina轉(zhuǎn)錄因子,，與過敏癥發(fā)病密切相關(guān)的細(xì)胞因子——白介素4的生成被抑制。與此相對照的是,，屬于過敏體質(zhì)的實(shí)驗(yàn)鼠體內(nèi)T細(xì)胞中的Mina轉(zhuǎn)錄因子相當(dāng)少,，白介素4的產(chǎn)生不能被抑制,，因而容易過敏。
攜帶人體遺傳信息的DNA由4個不同堿基組合而成,。不同人的基因組之間的堿基排列順序大部分相同,，但也存在極小差異，有時(shí)只有單一堿基存在差異,，這種差異被稱為單核苷酸多態(tài)性,。單核苷酸多態(tài)性與患特定疾病相關(guān)，也可能使相同藥物對不同的人產(chǎn)生不同療效,。
在上述研究中,，科研人員發(fā)現(xiàn)實(shí)驗(yàn)鼠的過敏體質(zhì)由Mina轉(zhuǎn)錄因子基因的單核苷酸多態(tài)性決定，他們推測人體內(nèi)Mina轉(zhuǎn)錄因子基因的單核苷酸多態(tài)性也會導(dǎo)致人類出現(xiàn)容易過敏和不易過敏的差異,。
相關(guān)研究成果刊登在最新一期英國《自然－免疫學(xué)》雜志上,。（生物谷Bioon.com）
生物谷推薦原始出處：
Nature Immunology 10, 872 - 879 (2009) 28 June 2009 | Corrected online: 5 July 2009 | doi:10.1038/ni.1747
Mina, an Il4 repressor, controls T helper type 2 bias
Mariko Okamoto1,5, Melanie Van Stry2,5, Linda Chung2, Madoka Koyanagi2, Xizhang Sun3, Yoshie Suzuki1, Osamu Ohara4, Hiroshi Kitamura4, Atsushi Hijikata4, Masato Kubo1 & Mark Bix2
Abstract
T helper type 2 (TH2) bias, which is the propensity of naive CD4+ T cells to differentiate into interleukin 4 (IL-4)-secreting TH2 cells, is a genetic trait that affects susceptibility to infectious, autoimmune and allergic diseases. TH2 bias correlates with the amount of IL-4 initially secreted by newly activated helper T cells that feeds back positively through the pathway of the IL-4 receptor and the transcription factors STAT6 and GATA-3 to drive TH2 development. Here we identify Mina, a member of the jumonji C (JmjC) protein family, as a genetic determinant of TH2 bias. Mina specifically bound to and repressed the Il4 promoter. Mina overexpression in transgenic mice impaired Il4 expression, whereas its knockdown in primary CD4+ T cells led to Il4 derepression. Our findings collectively provide mechanistic insight into an Il4-regulatory pathway that controls helper T cell differentiation and genetic variation in TH2 bias.
1 Laboratory for Signal Network, Research Center for Allergy and Immunology, RIKEN Yokohama Institute, Yokohama, Japan.
2 Department of Immunology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
3 Department of Immunology, University of Washington, Seattle, Washington, USA.
4 Laboratory for Immunogenomics, Research Center for Allergy and Immunology, RIKEN Yokohama Institute, Yokohama, Japan.
5 These authors contributed equally to this work.
