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*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

43 Scopus citations

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 languageAmerican English
Pages (from-to)481-500
Number of pages20
JournalJournal of Experimental Medicine
Volume215
Issue number2
DOIs
StatePublished - 1 Feb 2018
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2018 Capucha et al.

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