Development of intestinal M cells and follicle-associated epithelium is regulated by TRAF6-mediated NF-κB signaling.
Development of intestinal M cells and follicle-associated epithelium is regulated by TRAF6-mediated NF-κB signaling.
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DOI：
10.1084/jem.20160659
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发表时间：
2018-02-05
期刊：
影响因子：
--
通讯作者：
Ohno H
中科院分区：
文献类型：
--
作者：
Kanaya T;Sakakibara S;Jinnohara T;Hachisuka M;Tachibana N;Hidano S;Kobayashi T;Kimura S;Iwanaga T;Nakagawa T;Katsuno T;Kato N;Akiyama T;Sato T;Williams IR;Ohno H
TRAF 6对RANK介导的NF-κB活化至关重要，并参与多种类型细胞的发育。Kanaya et al.证明RANK-TRAF 6介导的NF-κB对M细胞和FAE的发育至关重要。M细胞位于覆盖派尔集合淋巴结（PP）的滤泡相关上皮（FAE）中，负责肠道抗原的摄取。M细胞的分化是由NF-κB受体激活剂启动的。然而，参与M细胞分化的细胞内途径仍然是难以捉摸的。在这项研究中，我们证明了由RANK激活的NF-κB通路对于使用体外类器官培养的M细胞分化是必需的。NF-κB转录因子的过表达增强了M细胞相关分子的表达，但不足以完成M细胞分化。此外，我们评估了肿瘤坏死因子受体相关因子6（TRAF 6）的需求。肠上皮中TRAF 6的条件性缺失导致PP中M细胞的完全丧失，导致PP中抗原摄取受损。此外，FAE相关基因的表达在TRAF 6缺陷小鼠中几乎沉默。因此，本研究证明了TRAF 6介导的NF-κB信号在M细胞和FAE的发展中的关键作用。
TRAF6 is essential for RANK-mediated NF-κB activation and is involved in the development of several types of cells. Kanaya et al. demonstrate that RANK–TRAF6-mediated NF-κB is essential for the development of M cells and FAE. M cells are located in the follicle-associated epithelium (FAE) that covers Peyer’s patches (PPs) and are responsible for the uptake of intestinal antigens. The differentiation of M cells is initiated by receptor activator of NF-κB. However, the intracellular pathways involved in M cell differentiation are still elusive. In this study, we demonstrate that the NF-κB pathway activated by RANK is essential for M cell differentiation using in vitro organoid culture. Overexpression of NF-κB transcription factors enhances the expression of M cell–associated molecules but is not sufficient to complete M cell differentiation. Furthermore, we evaluated the requirement for tumor necrosis factor receptor–associated factor 6 (TRAF6). Conditional deletion of TRAF6 in the intestinal epithelium causes a complete loss of M cells in PPs, resulting in impaired antigen uptake into PPs. In addition, the expression of FAE-associated genes is almost silenced in TRAF6-deficient mice. This study thus demonstrates the crucial role of TRAF6-mediated NF-κB signaling in the development of M cells and FAE.
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DOI：
10.1084/jem.20141207
发表时间：
2014-11-17
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Akiyama N;Shinzawa M;Miyauchi M;Yanai H;Tateishi R;Shimo Y;Ohshima D;Matsuo K;Sasaki I;Hoshino K;Wu G;Yagi S;Inoue J;Kaisho T;Akiyama T
通讯作者：
Akiyama T
DOI：
10.1084/jem.20160770
发表时间：
2017-06-05
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Jinnohara T;Kanaya T;Hase K;Sakakibara S;Kato T;Tachibana N;Sasaki T;Hashimoto Y;Sato T;Watarai H;Kunisawa J;Shibata N;Williams IR;Kiyono H;Ohno H
通讯作者：
Ohno H
影响因子：
5.3
作者：
de Lau, Wim;Kujala, Pekka;Clevers, Hans
通讯作者：
Clevers, Hans
影响因子：
1.5
作者：
Kawano, Kazuya;Ebisawa, Masashi;Ohno, Hiroshi
通讯作者：
Ohno, Hiroshi
影响因子：
56.9
作者：
Akiyama, T;Maeda, S;Inoue, J
通讯作者：
Inoue, J