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

Tal Capucha; Noam Koren; Maria Nassar; Oded Heyman; Tsipora Nir; Maayan Levy; Gili Zilberman-Schapira; Katya Zelentova; Luba Eli-Berchoer; Martin Zenke; Thomas Hieronymus; Asaf Wilensky; Herve Bercovier; Eran Elinav; Björn E. Clausen; Avi Hai Hovav

doi:10.1084/jem.20171508

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

Tal Capucha, Noam Koren, Maria Nassar, Oded Heyman, Tsipora Nir, Maayan Levy, Gili Zilberman-Schapira, Katya Zelentova, Luba Eli-Berchoer, Martin Zenke, Thomas Hieronymus, Asaf Wilensky, Herve Bercovier, Eran Elinav, Björn E. Clausen, Avi Hai Hovav

The Hebrew University of Jerusalem, Weizmann Institute of Science

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Pages (from-to)	481-500
Number of pages	20
Journal	Journal of Experimental Medicine
Volume	215
Issue number	2
DOIs	https://doi.org/10.1084/jem.20171508
State	Published - 1 Feb 2018

All Science Journal Classification (ASJC) codes

Immunology and Allergy
Immunology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1084/jem.20171508

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Capucha, T., Koren, N., Nassar, M., Heyman, O., Nir, T., Levy, M., Zilberman-Schapira, G., Zelentova, K., Eli-Berchoer, L., Zenke, M., Hieronymus, T., Wilensky, A., Bercovier, H., Elinav, E., Clausen, B. E., & Hovav, A. H. (2018). Sequential BMP7/TGF-β1 signaling and microbiota instruct mucosal Langerhans cell differentiation. Journal of Experimental Medicine, 215(2), 481-500. https://doi.org/10.1084/jem.20171508

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title = "Sequential BMP7/TGF-β1 signaling and microbiota instruct mucosal Langerhans cell differentiation",

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.",

author = "Tal Capucha and Noam Koren and Maria Nassar and Oded Heyman and Tsipora Nir and Maayan Levy and Gili Zilberman-Schapira and Katya Zelentova and Luba Eli-Berchoer and Martin Zenke and Thomas Hieronymus and Asaf Wilensky and Herve Bercovier and Eran Elinav and Clausen, \{Bj{\"o}rn E.\} and Hovav, \{Avi Hai\}",

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year = "2018",

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day = "1",

doi = "10.1084/jem.20171508",

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Capucha, T, Koren, N, Nassar, M, Heyman, O, Nir, T, Levy, M, Zilberman-Schapira, G, Zelentova, K, Eli-Berchoer, L, Zenke, M, Hieronymus, T, Wilensky, A, Bercovier, H, Elinav, E, Clausen, BE & Hovav, AH 2018, 'Sequential BMP7/TGF-β1 signaling and microbiota instruct mucosal Langerhans cell differentiation', Journal of Experimental Medicine, vol. 215, no. 2, pp. 481-500. https://doi.org/10.1084/jem.20171508

TY - JOUR

T1 - Sequential BMP7/TGF-β1 signaling and microbiota instruct mucosal Langerhans cell differentiation

AU - Capucha, Tal

AU - Koren, Noam

AU - Nassar, Maria

AU - Heyman, Oded

AU - Nir, Tsipora

AU - Levy, Maayan

AU - Zilberman-Schapira, Gili

AU - Zelentova, Katya

AU - Eli-Berchoer, Luba

AU - Zenke, Martin

AU - Hieronymus, Thomas

AU - Wilensky, Asaf

AU - Bercovier, Herve

AU - Elinav, Eran

AU - Clausen, Björn E.

AU - Hovav, Avi Hai

PY - 2018/2/1

Y1 - 2018/2/1

N2 - 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.

AB - 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.

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U2 - 10.1084/jem.20171508

DO - 10.1084/jem.20171508

M3 - مقالة

C2 - 29343501

SN - 0022-1007

VL - 215

SP - 481

EP - 500

JO - Journal of Experimental Medicine

JF - Journal of Experimental Medicine

IS - 2

ER -

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

Abstract

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