Crucial role of MLL for the maintenance of memory T helper type 2 cell responses
Crucial role of MLL for the maintenance of memory T helper type 2 cell responses
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DOI：
10.1016/j.immuni.2006.03.017
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发表时间：
2006-05-01
期刊：
影响因子：
32.4
通讯作者：
Nakayama, Toshinori
中科院分区：
文献类型：
--
作者：
Yamashita, Masakatsu;Hirahara, Kiyoshi;Nakayama, Toshinori
混合谱系白血病 (MLL) 基因是三胸果蝇的哺乳动物同源基因，参与调节 Hox 基因表达和造血功能的维持。 MLL 在免疫系统中的生理功能仍然很大程度上未知。尽管 MLL+/- CD4 T 细胞在体外正常分化为抗原特异性效应 Th1/Th2 细胞，但记忆 Th2 细胞产生 Th2 细胞因子的能力选择性降低。此外，Th2 细胞因子基因座的组蛋白修饰在 MLL+/- 记忆 Th2 细胞中没有得到正确维持。记忆 Th2 细胞中 MLL 表达的减少导致 GATA3 表达减少，并伴有 GATA3 位点组蛋白修饰受损。证明了 MLL 与 GATA3 基因座和 Th2 细胞因子基因座的直接关联。在 MLL+/- Th2 细胞移植小鼠中，记忆 Th2 细胞依赖性过敏性气道炎症减少。因此，表明 MLL 在维持记忆 Th2 细胞功能中发挥着至关重要的作用。
The Mixed-Lineage Leukemia (MLL) gene, a mammalian homolog of the Drosophila trithorax, is implicated in regulating the maintenance of Hox gene expression and hematopoiesis. The physiological functions of MLL in the immune system remain largely unknown. Although MLL+/- CD4 T cells differentiate normally into antigen-specific effector Th1/Th2 cells in vitro, the ability of memory Th2 cells to produce Th2 cyto-kines was selectively reduced. Furthermore, histone modifications at the Th2 cytokine gene loci were not properly maintained in MLL+/- memory Th2 cells. The reduced expression of MLL in memory Th2 cells resulted in decreased GATA3 expression accompanied with impaired GATA3 locus histone modifications. The direct association of MLL with the GATA3 locus and the Th2 cytokine gene loci was demonstrated. Memory Th2 cell-dependent allergic airway inflammation was decreased in MLL+/- Th2 cell-transferred mice. Thus, a crucial role for MLL in the maintenance of memory Th2 cell function is indicated.