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
N1 - Publisher Copyright:
© 2018 Capucha et al.
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.
UR - http://www.scopus.com/inward/record.url?scp=85041419171&partnerID=8YFLogxK
U2 - 10.1084/jem.20171508
DO - 10.1084/jem.20171508
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C2 - 29343501
AN - SCOPUS:85041419171
SN - 0022-1007
VL - 215
SP - 481
EP - 500
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
IS - 2
ER -
