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GATA-3 表达的调控在 CD4 谱系分化过程中。

Regulation of GATA-3 expression during CD4 lineage differentiation.

机构信息

Immunobiology and Cancer Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA.

出版信息

J Immunol. 2011 Apr 1;186(7):3892-8. doi: 10.4049/jimmunol.1003505. Epub 2011 Feb 25.

DOI:10.4049/jimmunol.1003505
PMID:21357543
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3074202/
Abstract

GATA-3 is necessary for the development of MHC class II-restricted CD4 T cells, and its expression is increased during positive selection of these cells. TCR signals drive this upregulation, but the signaling pathways that control this process are not well understood. Using genetic and pharmacological approaches, we show that GATA-3 upregulation during thymocyte-positive selection is the result of additive inputs from the Ras/MAPK and calcineurin pathways. This upregulation requires the presence of the transcription factor c-Myb. Furthermore, we show that TH-POK can also upregulate GATA-3 in double-positive thymocytes, suggesting the existence of a positive feedback loop that contributes to lock in the initial commitment to the CD4 lineage during differentiation.

摘要

GATA-3 对于 MHC Ⅱ类限制性 CD4 T 细胞的发育是必需的，并且其表达在这些细胞的阳性选择期间增加。TCR 信号驱动这种上调，但控制此过程的信号通路尚不清楚。使用遗传和药理学方法，我们表明 GATA-3 在胸腺细胞阳性选择期间的上调是 Ras/MAPK 和钙调神经磷酸酶途径的加性输入的结果。这种上调需要转录因子 c-Myb 的存在。此外，我们还表明，TH-POK 也可以在双阳性胸腺细胞中上调 GATA-3，这表明存在正反馈回路，有助于在分化过程中锁定对 CD4 谱系的初始承诺。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0426/3074202/22117c9db037/nihms267983f7.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0426/3074202/7143cb12baf5/nihms267983f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0426/3074202/78bd6e75f56f/nihms267983f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0426/3074202/3ee785a36c04/nihms267983f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0426/3074202/6ca16731bf12/nihms267983f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0426/3074202/22117c9db037/nihms267983f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0426/3074202/4eb433fce757/nihms267983f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0426/3074202/9d47e850f6f8/nihms267983f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0426/3074202/7143cb12baf5/nihms267983f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0426/3074202/78bd6e75f56f/nihms267983f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0426/3074202/3ee785a36c04/nihms267983f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0426/3074202/6ca16731bf12/nihms267983f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0426/3074202/22117c9db037/nihms267983f7.jpg

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The sequential activity of Gata3 and Thpok is required for the differentiation of CD1d-restricted CD4+ NKT cells.Gata3 和 Thpok 的顺序活性对于 CD1d 限制性 CD4+ NKT 细胞的分化是必需的。
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