Macrophage-derived IL-10 mediates mucosal repair by epithelial WISP-1 signaling
| Autor: | Priya H. Dedhia, Mingli Feng, Roland Hilgarth, Hikaru Nishio, Charles A. Parkos, Timothy L. Denning, Giovanna Leoni, Monique N. O’Leary, Dorothee Siuda, Asma Nusrat, Holly C. Williams, Jennifer C. Brazil, Veronica Azcutia, Miguel Quiros, Vicky Garcia-Hernandez, Philipp Neumann, Gabriela Bernal, Christian Gerner-Smidt, Jason R. Spence |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Colon T cell Inflammation Biology CREB CCN Intercellular Signaling Proteins Mice 03 medical and health sciences 0302 clinical medicine Immune system Intestinal mucosa Proto-Oncogene Proteins medicine Animals Humans Intestinal Mucosa Cyclic AMP Response Element-Binding Protein Cell Proliferation Mice Knockout Wound Healing Innate immune system CD11 Antigens Macrophages Epithelial Cells General Medicine Interleukin-10 Cell biology Mice Inbred C57BL Interleukin 10 030104 developmental biology medicine.anatomical_structure Gene Expression Regulation 030220 oncology & carcinogenesis biology.protein medicine.symptom Wound healing Gene Deletion Research Article Signal Transduction |
| Zdroj: | Journal of Clinical Investigation. 127:3510-3520 |
| ISSN: | 1558-8238 0021-9738 |
| DOI: | 10.1172/jci90229 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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