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连续的 BMP7/TGF-β1 信号和微生物群落指导黏膜朗格汉斯细胞分化。

Sequential BMP7/TGF-β1 signaling and microbiota instruct mucosal Langerhans cell differentiation.

机构信息

The Institute of Dental Sciences, Hebrew University-Hadassah Medical Center, Jerusalem, Israel.

Department of Periodontology, Faculty of Dental Medicine, Hebrew University-Hadassah Medical Center, Jerusalem, Israel.

出版信息

J Exp Med. 2018 Feb 5;215(2):481-500. doi: 10.1084/jem.20171508. Epub 2018 Jan 17.

DOI:10.1084/jem.20171508
PMID:29343501
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5789418/
Abstract

Mucosal Langerhans cells (LCs) originate from pre-dendritic cells and monocytes. However, the mechanisms involved in their in situ development remain unclear. Here, we demonstrate that the differentiation of murine mucosal LCs is a two-step process. In the lamina propria, signaling via BMP7-ALK3 promotes translocation of LC precursors to the epithelium. Within the epithelium, TGF-β1 finalizes LC differentiation, and ALK5 is crucial to this process. Moreover, the local microbiota has a major impact on the development of mucosal LCs, whereas LCs in turn maintain mucosal homeostasis and prevent tissue destruction. These results reveal the differential and sequential role of TGF-β1 and BMP7 in LC differentiation and highlight the intimate interplay of LCs with the microbiota.

摘要

黏膜朗格汉斯细胞（LCs）起源于前树突状细胞和单核细胞。然而，其原位发育的机制尚不清楚。在这里，我们证明了小鼠黏膜 LCs 的分化是一个两步过程。在固有层中，BMP7-ALK3 信号通路促进 LC 前体向上皮细胞的迁移。在上皮细胞中，TGF-β1 最终完成 LC 的分化，ALK5 对这一过程至关重要。此外，局部微生物群对黏膜 LCs 的发育有重大影响，而 LCs 反过来又维持黏膜的稳态并防止组织破坏。这些结果揭示了 TGF-β1 和 BMP7 在 LC 分化中的差异和顺序作用，并强调了 LCs 与微生物群之间的密切相互作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c409/5789418/f834f6c1a6ff/JEM_20171508_Fig9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c409/5789418/7591930ca29d/JEM_20171508_Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c409/5789418/093466595b31/JEM_20171508_Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c409/5789418/582289dd1192/JEM_20171508_Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c409/5789418/1c940d5d3c92/JEM_20171508_Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c409/5789418/4957a3c0e5e4/JEM_20171508_Fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c409/5789418/31b3dcc42d0b/JEM_20171508_Fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c409/5789418/4a95b0bc8263/JEM_20171508_Fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c409/5789418/66c447d9b070/JEM_20171508_Fig8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c409/5789418/f834f6c1a6ff/JEM_20171508_Fig9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c409/5789418/7591930ca29d/JEM_20171508_Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c409/5789418/093466595b31/JEM_20171508_Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c409/5789418/582289dd1192/JEM_20171508_Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c409/5789418/1c940d5d3c92/JEM_20171508_Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c409/5789418/4957a3c0e5e4/JEM_20171508_Fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c409/5789418/31b3dcc42d0b/JEM_20171508_Fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c409/5789418/4a95b0bc8263/JEM_20171508_Fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c409/5789418/66c447d9b070/JEM_20171508_Fig8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c409/5789418/f834f6c1a6ff/JEM_20171508_Fig9.jpg

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