TY - JOUR AU - Quiros, Miguel AU - Nishio, Hikaru AU - Neumann, Philipp A. AU - Siuda, Dorothee AU - Brazil, Jennifer C. AU - Azcutia, Veronica AU - Hilgarth, Roland AU - O’Leary, Monique N. AU - Garcia-Hernandez, Vicky AU - Leoni, Giovanna AU - Feng, Mingli AU - Bernal, Gabriela AU - Williams, Holly AU - Dedhia, Priya H. AU - Gerner-Smidt, Christian AU - Spence, Jason AU - Parkos, Charles A. AU - Denning, Timothy L. AU - Nusrat, Asma T1 - Macrophage-derived IL-10 mediates mucosal repair by epithelial WISP-1 signaling PY - 2017/11/15/ AB - 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. JF - The Journal of Clinical Investigation JA - J Clin Invest SN - 0021-9738 DO - 10.1172/JCI90229 VL - 127 IS - 9 UR - https://doi.org/10.1172/JCI90229 SP - 3510 EP - 3520 PB - The American Society for Clinical Investigation ER -