Sequential BMP7/TGF-?1 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-?1 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-?1 and BMP7 in LC differentiation and highlight the intimate interplay of LCs with the microbiota.

SUBMITTER: Capucha T 

PROVIDER: S-EPMC5789418 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature