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

• DOI: 10.1084/jem.20171508
• Publication Date: 2018-01-17T14:25:17Z
• Authors: Tal Capucha; Noam Koren; Maria Nassar; Oded Heyman; Tsipora Nir; Maayan Levy; Gili Zilberman-Sc...; Katya Zelentova; Luba Eli-Berchoer; Martin Zenke; Thomas Hieronymus; Asaf Wilensky; Herve Bercovier; Eran Elinav; Björn E. Clausen; Avi-Hai Hovav
• Keywords: Lamina propria

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