RT Journal Article
T1 Macrophage-derived IL-10 mediates mucosal repair by epithelial WISP-1 signaling
A1 Azcutia Criado, Verónica
A1 Quirós, Miguel
A1 Nishio, Hikaru
A1 Neumann, Philipp A.
A1 Siuda, Dorothee
A1 Brazil, Jennifer C.
A1 Hilgart, R.
A1 O'Leary, Monique N.
A1 Garcia-Hernandez, Vicky
A1 Leoni, Giovanna
A1 Feng, Mingli
A1 Bernal, Gabriela
A1 Williams, Holly
A1 Dedhia, Priya H.
A1 Gerner-Smidt, Christiam
A1 Spence, Jason
A1 Parkos Charles A., 
A1 Denning, Timothy L.
A1 Nusrat, Asma
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. Consistentwith 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.
PB Amer Soc Clinical Investigation Inc.
YR 2017
FD 2017
LK https://hdl.handle.net/20.500.14352/116940
UL https://hdl.handle.net/20.500.14352/116940
LA eng
NO Quiros, Miguel, et al. «Macrophage-Derived IL-10 Mediates Mucosal Repair by Epithelial WISP-1 Signaling». The Journal of Clinical Investigation, vol. 127, n.o 9, noviembre de 2017, pp. 3510-20. www.jci.org, https://doi.org/10.1172/JCI90229
NO Natioanl Institues of Health (NIH)
NO Crohn’s and Colitis Foundation of America
NO German Research Foundation (DFG)
DS Docta Complutense
RD 11 abr 2025