ADAM17-deficiency on microglia but not on macrophages promotes phagocytosis and functional recovery after spinal cord injury

Publication date: Available online 6 March 2019Source: Brain, Behavior, and ImmunityAuthor(s): Daniela Sommer, Inge Corstjens, Selien Sanchez, Dearbhaile Dooley, Stefanie Lemmens, Jana Van Broeckhoven, Jeroen Bogie, Tim Vanmierlo, Pia M Vidal, Stefan Rose-John, Myriam Gou-Fabregas, Sven HendrixAbstractA 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 chimeras 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.Graphical...
Source: Brain, Behavior, and Immunity - Category: Neurology Source Type: research