日本理化研究所近日發(fā)表新聞公報說,其研究人員與美國同行經(jīng)動物實驗發(fā)現(xiàn),,負責合成轉錄因子Mina的基因存在單核苷酸多態(tài)性,這一特點與過敏癥發(fā)病相關。
有的人容易過敏,有的人則不易過敏,,醫(yī)學界普遍認為過敏體質(zhì)與遺傳有關,但迄今尚未完全了解導致過敏體質(zhì)的基因和具體機制,。
新聞公報說,理化研究所免疫,、過敏科學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構的同行,,對比了屬于過敏體質(zhì)的實驗鼠和不易過敏的實驗鼠,發(fā)現(xiàn)它們體內(nèi)負責指導合成轉錄因子Mina的基因存在多處單核苷酸多態(tài)性,。其結果,,不易過敏的實驗鼠體內(nèi)T細胞中存在大量Mina轉錄因子,與過敏癥發(fā)病密切相關的細胞因子——白介素4的生成被抑制,。與此相對照的是,,屬于過敏體質(zhì)的實驗鼠體內(nèi)T細胞中的Mina轉錄因子相當少,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,,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)實驗鼠的過敏體質(zhì)由Mina轉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轉錄因子基因的單核苷酸多態(tài)性也會導致人類出現(xiàn)容易過敏和不易過敏的差異,。
相關研究成果刊登在最新一期英國《自然-免疫學》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.