@article{4fbf6938bf9749ef9951a0193d5118c4,
title = "ADAM17-deficiency on microglia but not on macrophages promotes phagocytosis and functional recovery after spinal cord injury",
abstract = "A disintegrin and metalloproteinase 17 (ADAM17) is the major sheddase involved in the cleavage of a plethora of cytokines, cytokine receptors and growth factors, thereby playing a substantial role in inflammatory and regenerative processes after central nervous system trauma. By making use of a hypomorphic ADAM17 knockin mouse model as well as pharmacological ADAM10/ADAM17 inhibitors, we showed that ADAM17-deficiency or inhibition significantly increases clearance of apoptotic cells, promotes axon growth and improves functional recovery after spinal cord injury (SCI) in mice. Microglia-specific ADAM17-knockout (ADAM17flox(+/+)-Cx3Cr1 Cre(+/-)) mice also showed improved functional recovery similar to hypomorphic ADAM17 mice. In contrast, endothelial-specific (ADAM17flox(+/+)-Cdh5Pacs Cre(+/-)) and macrophage-specific (ADAM17flox(+/+)-LysM Cre(+/-)) ADAM17-knockout mice or bone marrow chimera with transplanted ADAM17-deficient macrophages, displayed no functional improvement compared to wild type mice. These data indicate that ADAM17 expression on microglia cells (and not on macrophages or endothelial cells) plays a detrimental role in inflammation and functional recovery after SCI.",
keywords = "ADAM17, Inflammation, Macrophages, Microglia, Spinal cord injury, MAST-CELLS PROTECT, TNF-ALPHA, ALTERNATIVE ACTIVATION, INFLAMMATORY RESPONSE, CNS REMYELINATION, UP-REGULATION, REGENERATION, DISINTEGRIN, EXPRESSION",
author = "Daniela Sommer and Inge Corstjens and Selien Sanchez and Dearbhaile Dooley and Stefanie Lemmens and \{Van Broeckhoven\}, Jana and Jeroen Bogie and Tim Vanmierlo and Vidal, \{Pia M.\} and Stefan Rose-John and Myriam Gou-Fabregas and Sven Hendrix",
note = "Funding Information: The authors thank Prof. Dr. Erik Boddeke ( University of Groningen ) for his advice and Dr. Leen Timmermans ( Hasselt University ) for help with the immunohistochemistry. This study was supported by Fonds voor Wetenschappelijk Onderzoek Vlaanderen ( FWO ; GOA1413 , GOA5813FWO , GO6677 to SH and 11ZQ5.16N to DS). The work of SRJ was supported by the Deutsche Forschungsgemeinschaft (Bonn, Germany) Grant CRC877 (Project A1, and the German Cluster of Excellence 306, 'Inflammation at Interfaces'). Funding Information: The authors thank Prof. Dr. Erik Boddeke (University of Groningen) for his advice and Dr. Leen Timmermans (Hasselt University) for help with the immunohistochemistry. This study was supported by Fonds voor Wetenschappelijk Onderzoek Vlaanderen (FWO; GOA1413, GOA5813FWO, GO6677 to SH and 11ZQ5.16N to DS). The work of SRJ was supported by the Deutsche Forschungsgemeinschaft (Bonn, Germany) Grant CRC877 (Project A1, and the German Cluster of Excellence 306, {\textquoteleft}Inflammation at Interfaces{\textquoteright}). Publisher Copyright: {\textcopyright} 2019 The Authors",
year = "2019",
month = aug,
doi = "10.1016/j.bbi.2019.02.032",
language = "English",
volume = "80",
pages = "129--145",
journal = "Brain Behavior and Immunity",
issn = "0889-1591",
publisher = "Academic Press Inc.",
}