2. Academic Validation
  3. ADAM17-deficiency on microglia but not on macrophages promotes phagocytosis and functional recovery after spinal cord injury

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

  • Brain Behav Immun. 2019 Aug;80:129-145. doi: 10.1016/j.bbi.2019.02.032.
Daniela Sommer 1,  Inge Corstjens 1,  Selien Sanchez 1,  Dearbhaile Dooley 2,  Stefanie Lemmens 1,  Jana Van Broeckhoven 1,  Jeroen Bogie 1,  Tim Vanmierlo 3,  Pia M Vidal 4,  Stefan Rose-John 5,  Myriam Gou-Fabregas 1,  Sven Hendrix 6
Affiliations

Affiliations

  • 1 Biomedical Research Institute, Hasselt University, 3500 Hasselt, Belgium.
  • 2 Health Science Centre, School of Medicine, University College Dublin, Dublin 4, Ireland.
  • 3 Biomedical Research Institute, Hasselt University, 3500 Hasselt, Belgium; Division of Translational Neuroscience, MHeNs, Maastricht University, 6229ER Maastricht, the Netherlands.
  • 4 Laboratory of Neuroimmunology, Fundación Ciencia & Vida, 7780272 Santiago, Chile.
  • 5 Institute of Biochemistry, Christian-Albrechts University Kiel, 24098 Kiel, Germany.
  • 6 Biomedical Research Institute, Hasselt University, 3500 Hasselt, Belgium. Electronic address: [email protected].
PMID: 30851378 DOI: 10.1016/j.bbi.2019.02.032
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.

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