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IKZF3/Aiolos 与 CD4 T 细胞表达的 IL-10 相关，但不足以使其表达。

IKZF3/Aiolos Is Associated with but Not Sufficient for the Expression of IL-10 by CD4 T Cells.

机构信息

Centre for Inflammation Biology and Cancer Immunology, Department of Inflammation Biology, School of Immunology and Microbial Sciences, King's College London, London SE1 1UL, United Kingdom.

Department of Infectious Diseases, School of Immunology and Microbial Sciences, King's College London, Guy's Hospital, London SE1 9RT, United Kingdom; and.

出版信息

J Immunol. 2020 Jun 1;204(11):2940-2948. doi: 10.4049/jimmunol.1901283. Epub 2020 Apr 22.

DOI:10.4049/jimmunol.1901283
PMID:32321757
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7231851/
Abstract

The expression of anti-inflammatory IL-10 by CD4 T cells is indispensable for immune homeostasis, as it allows T cells to moderate their effector function. We previously showed that TNF-α blockade during T cell stimulation in CD4 T cell/monocyte cocultures resulted in maintenance of IL-10-producing T cells and identified IKZF3 as a putative regulator of IL-10. In this study, we tested the hypothesis that IKZF3 is a transcriptional regulator of IL-10 using a human CD4 T cell-only culture system. IL-10 CD4 T cells expressed the highest levels of IKZF3 both ex vivo and after activation compared with IL-10-CD4 T cells. Pharmacological targeting of IKZF3 with the drug lenalidomide showed that IKZF3 is required for anti-CD3/CD28 mAb-mediated induction of IL-10 but is dispensable for ex vivo IL-10 expression. However, overexpression of IKZF3 was unable to upregulate IL-10 at the mRNA or protein level in CD4 T cells and did not drive the transcription of the promoter or putative local enhancer constructs. Collectively, these data indicate that IKZF3 is associated with but not sufficient for IL-10 expression in CD4 T cells.

摘要

CD4 T 细胞中抗炎性白细胞介素 10（IL-10）的表达对于免疫稳态是不可或缺的，因为它允许 T 细胞调节其效应功能。我们之前曾表明，在 CD4 T 细胞/单核细胞共培养物中 T 细胞刺激期间阻断 TNF-α会导致产生 IL-10 的 T 细胞得以维持，并确定 IKZF3 是 IL-10 的一个潜在调节因子。在这项研究中，我们使用仅含人 CD4 T 细胞的培养系统来测试 IKZF3 是 IL-10 的转录调节剂的假说。与 IL-10-CD4 T 细胞相比，IL-10 CD4 T 细胞在体外和激活后表达最高水平的 IKZF3。用药物来那度胺对 IKZF3 进行药理学靶向显示，IKZF3 是抗 CD3/CD28 mAb 介导的 IL-10 诱导所必需的，但对于体外 IL-10 表达是可有可无的。然而，在 CD4 T 细胞中过表达 IKZF3 不能上调 IL-10 的 mRNA 或蛋白水平，也不能驱动启动子或假定的局部增强子构建体的转录。总而言之，这些数据表明，IKZF3 与 CD4 T 细胞中的 IL-10 表达相关，但不足以驱动其表达。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8bd1/7231851/284e2e9fe380/ji1901283f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8bd1/7231851/9a6188ec075a/ji1901283absf1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8bd1/7231851/723621188faf/ji1901283f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8bd1/7231851/b49219f0b552/ji1901283f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8bd1/7231851/de4925878e58/ji1901283f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8bd1/7231851/1bcb21058416/ji1901283f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8bd1/7231851/284e2e9fe380/ji1901283f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8bd1/7231851/9a6188ec075a/ji1901283absf1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8bd1/7231851/723621188faf/ji1901283f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8bd1/7231851/b49219f0b552/ji1901283f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8bd1/7231851/de4925878e58/ji1901283f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8bd1/7231851/1bcb21058416/ji1901283f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8bd1/7231851/284e2e9fe380/ji1901283f5.jpg

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