MicroRNA-29 regulates T-box transcription factors and interferon-γ production in helper T cells.
MicroRNA-29 regulates T-box transcription factors and interferon-γ production in helper T cells.
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DOI：
10.1016/j.immuni.2011.07.009
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发表时间：
2011-08-26
期刊：
影响因子：
32.4
通讯作者：
Ansel KM
中科院分区：
文献类型：
--
作者：
Steiner DF;Thomas MF;Hu JK;Yang Z;Babiarz JE;Allen CD;Matloubian M;Blelloch R;Ansel KM
MicroRNA（miRNA）缺陷型辅助性T细胞表现出IFN-γ产生异常和增殖降低。然而，单个miRNA对这种表型的贡献仍然知之甚少。我们在原代T细胞中进行了miRNA功能的筛选，并鉴定了挽救与miRNA缺陷相关的缺陷的单个miRNA。miR-17和miR-92家族的多个成员增强了miRNA缺陷的T细胞增殖，而miR-29在很大程度上纠正了它们异常的干扰素-γ（IFN-γ）表达。miR-29对IFN-γ产生的抑制涉及直接靶向T-bet和Eomes，这两种转录因子已知诱导IFN-γ产生。虽然在辅助性T细胞中通常不以功能相关的量表达，但Eomes在miRNA缺陷型细胞中丰富，并且在野生型细胞中miR-29抑制后上调。这些结果表明，miR-29通过抑制多个靶基因来调节辅助性T细胞分化，所述靶基因包括至少两个能够独立地诱导辅助性T细胞1（Th 1）细胞基因表达程序的靶基因。
MicroRNA (miRNA)-deficient helper T cells exhibit abnormal IFN-γ production and decreased proliferation. However, the contributions of individual miRNAs to this phenotype remain poorly understood. We conducted a screen for miRNA function in primary T cells and identified individual miRNAs that rescue the defects associated with miRNA deficiency. Multiple members of the miR-17 and miR-92 families enhanced miRNA-deficient T cell proliferation whereas miR-29 largely corrected their aberrant interferon-γ (IFN-γ) expression. Repression of IFN-γ production by miR-29 involved direct targeting of both T-bet and Eomes, two transcription factors known to induce IFN-γ production. Although not usually expressed at functionally relevant amounts in helper T cells, Eomes was abundant in miRNA-deficient cells and was upregulated after miR-29 inhibition in wild-type cells. These results demonstrate that miR-29 regulates helper T cell differentiation by repressing multiple target genes, including at least two that are independently capable of inducing the T helper 1 (Th1) cell gene expression program.
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DOI：
10.1084/jem.20061692
发表时间：
2006-10-30
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Cobb BS;Hertweck A;Smith J;O'Connor E;Graf D;Cook T;Smale ST;Sakaguchi S;Livesey FJ;Fisher AG;Merkenschlager M
通讯作者：
Merkenschlager M
影响因子：
10.5
作者：
Babiarz, Joshua E.;Ruby, J. Graham;Blelloch, Robert
通讯作者：
Blelloch, Robert
影响因子：
7
作者：
Barski, Artem;Jothi, Raja;Zhao, Keji
通讯作者：
Zhao, Keji
影响因子：
14.9
作者：
Betel D;Wilson M;Gabow A;Marks DS;Sander C
通讯作者：
Sander C
影响因子：
56.9
作者：
Finotto, S;Neurath, MF;Glimcher, LH
通讯作者：
Glimcher, LH