Macrophage-derived IL-10 mediates mucosal repair by epithelial WISP-1 signaling

In response to injury, epithelial cells migrate and proliferate to cover denuded mucosal surfaces and repair the barrier defect. This process is orchestrated by dynamic crosstalk between immune cells and the epithelium; however, the mechanisms involved remain incompletely understood. Here, we report...

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Bibliographic Details
Authors: Azcutia Criado, Verónica, Quirós, Miguel, Nishio, Hikaru, Neumann, Philipp A., Siuda, Dorothee, Brazil, Jennifer C., Hilgart, R., O'Leary, Monique N., Garcia-Hernandez, Vicky, Leoni, Giovanna, Feng, Mingli, Bernal, Gabriela, Williams, Holly, Dedhia, Priya H., Gerner-Smidt, Christiam, Spence, Jason, Parkos Charles A., Denning, Timothy L., Nusrat, Asma
Format: article
Publication Date:2017
Country:España
Institution:Universidad Complutense de Madrid (UCM)
Repository:Docta Complutense
Language:English
OAI Identifier:oai:docta.ucm.es:20.500.14352/116940
Online Access:https://hdl.handle.net/20.500.14352/116940
Access Level:Open access
Keyword:612
Mucosal repair
IL-10
Intestinal epithelium
Macrophages
Fisiología animal (Farmacia)
24 Ciencias de la Vida
Description
Summary:In response to injury, epithelial cells migrate and proliferate to cover denuded mucosal surfaces and repair the barrier defect. This process is orchestrated by dynamic crosstalk between immune cells and the epithelium; however, the mechanisms involved remain incompletely understood. Here, we report that IL-10 was rapidly induced following intestinal mucosal injury and was required for optimal intestinal mucosal wound closure. Conditional deletion of IL-10 specifically in CD11c-expressing cells in vivo implicated macrophages as a critical innate immune contributor to IL-10–induced wound closure. Consistent with these findings, wound closure in T cell– and B cell–deficient Rag1–/– mice was unimpaired, demonstrating that adaptive immune cells are not absolutely required for this process. Further, following mucosal injury, macrophage-derived IL-10 resulted in epithelial cAMP response element–binding protein (CREB) activation and subsequent synthesis and secretion of the pro-repair WNT1-inducible signaling protein 1 (WISP-1). WISP-1 induced epithelial cell proliferation and wound closure by activating epithelial pro-proliferative pathways. These findings define the involvement of macrophages in regulating an IL-10/ CREB/WISP-1 signaling axis, with broad implications in linking innate immune activation to mucosal wound repair.

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