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AP-1 转录因子 c-Jun 和 JunB 对于 CD8α 常规树突状细胞的特性是必需的。

The AP-1 transcription factors c-Jun and JunB are essential for CD8α conventional dendritic cell identity.

机构信息

Institute of Cancer Research, Department of Medicine I, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.

Department of Microbiology, Immunobiology and Genetics, Max Perutz Labs, University of Vienna, Vienna, Austria.

出版信息

Cell Death Differ. 2021 Aug;28(8):2404-2420. doi: 10.1038/s41418-021-00765-4. Epub 2021 Mar 23.

DOI:10.1038/s41418-021-00765-4
PMID:33758366
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8329169/
Abstract

Dendritic cell (DC) development is orchestrated by lineage-determining transcription factors (TFs). Although, members of the activator-protein-1 (AP-1) family, including Batf3, have been implicated in conventional (c)DC specification, the role of Jun proteins is poorly understood. Here, we identified c-Jun and JunB as essential for cDC1 fate specification and function. In mice, Jun proteins regulate extrinsic and intrinsic pathways, which control CD8α cDC1 diversification, whereas CD103 cDC1 development is unaffected. The loss of c-Jun and JunB in DC progenitors diminishes the CD8α cDC1 pool and thus confers resistance to Listeria monocytogenes infection. Their absence in CD8α cDC1 results in impaired TLR triggering and antigen cross-presentation. Both TFs are required for the maintenance of the CD8α cDC1 subset and suppression of cDC2 identity on a transcriptional and phenotypic level. Taken together, these results demonstrate the essential role of c-Jun and JunB in CD8α cDC1 diversification, function, and maintenance of their identity.

摘要

树突状细胞 (DC) 的发育是由谱系决定的转录因子 (TFs) 调控的。虽然激活蛋白-1 (AP-1) 家族的成员，包括 Batf3，已被牵连到常规 (c)DC 的特化中，但 Jun 蛋白的作用知之甚少。在这里，我们确定 c-Jun 和 JunB 对于 cDC1 命运的特化和功能是必不可少的。在小鼠中，Jun 蛋白调节控制 CD8α cDC1 多样化的外在和内在途径，而 CD103 cDC1 的发育不受影响。DC 前体细胞中 c-Jun 和 JunB 的缺失会减少 CD8α cDC1 池，从而赋予对李斯特菌感染的抗性。它们在 CD8α cDC1 中的缺失导致 TLR 触发和抗原交叉呈递受损。这两种 TF 在 CD8α cDC1 的维持和抑制 cDC2 特性的转录和表型水平上都是必需的。总之，这些结果表明 c-Jun 和 JunB 在 CD8α cDC1 的多样化、功能和特性的维持中起着至关重要的作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd80/8329169/b7b674af7dec/41418_2021_765_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd80/8329169/472d2d905e1e/41418_2021_765_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd80/8329169/62f278003254/41418_2021_765_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd80/8329169/767ec36812a7/41418_2021_765_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd80/8329169/33f7248ce982/41418_2021_765_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd80/8329169/ef9eac771945/41418_2021_765_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd80/8329169/9ef24496af99/41418_2021_765_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd80/8329169/b7b674af7dec/41418_2021_765_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd80/8329169/472d2d905e1e/41418_2021_765_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd80/8329169/62f278003254/41418_2021_765_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd80/8329169/767ec36812a7/41418_2021_765_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd80/8329169/33f7248ce982/41418_2021_765_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd80/8329169/ef9eac771945/41418_2021_765_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd80/8329169/9ef24496af99/41418_2021_765_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd80/8329169/b7b674af7dec/41418_2021_765_Fig7_HTML.jpg

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