日本理化研究所近日发表新闻公报说，其研究人员与美国同行经动物实验发现，负责合成转录因子Mina的基因存在单核苷酸多态性，这一特点与过敏症发病相关。
有的人容易过敏，有的人则不易过敏，医学界普遍认为过敏体质与遗传有关，但迄今尚未完全了解导致过敏体质的基因和具体机制。
新闻公报说，理化研究所免疫、过敏科学综合研究中心的研究人员与美国田纳西州一所儿童疾病研究机构的同行，对比了属于过敏体质的实验鼠和不易过敏的实验鼠，发现它们体内负责指导合成转录因子Mina的基因存在多处单核苷酸多态性。其结果，不易过敏的实验鼠体内T细胞中存在大量Mina转录因子，与过敏症发病密切相关的细胞因子——白介素4的生成被抑制。与此相对照的是，属于过敏体质的实验鼠体内T细胞中的Mina转录因子相当少，白介素4的产生不能被抑制，因而容易过敏。
携带人体遗传信息的DNA由4个不同碱基组合而成。不同人的基因组之间的碱基排列顺序大部分相同，但也存在极小差异，有时只有单一碱基存在差异，这种差异被称为单核苷酸多态性。单核苷酸多态性与患特定疾病相关，也可能使相同药物对不同的人产生不同疗效。
在上述研究中，科研人员发现实验鼠的过敏体质由Mina转录因子基因的单核苷酸多态性决定，他们推测人体内Mina转录因子基因的单核苷酸多态性也会导致人类出现容易过敏和不易过敏的差异。
相关研究成果刊登在最新一期英国《自然－免疫学》杂志上。（生物谷Bioon.com）
生物谷推荐原始出处：
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.
