Kallikrein 6 secreted by oligodendrocytes regulates the progression of experimental autoimmune encephalomyelitis

Glia
Yoshio BandoShigetaka Yoshida

Abstract

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS), and experimental autoimmune encephalomyelitis (EAE) is a well-established animal model of the disease. Here, we examined the pathophysiological role of Kallikrein 6 (Klk6), a serine protease produced by oligodendrocytes (OLs), in EAE using Klk6 knockout (Klk6-/-) mice. Compared with Klk6+/+ (wild-type) mice, Klk6-/- mice showed milder EAE symptoms, including delayed onset and milder paralysis. Loss of Klk6 suppressed matrix metalloprotease-9 expression and diminished the infiltration of peripheral inflammatory cells into the CNS by decreasing blood-brain barrier (BBB) permeability and reducing expression levels of inflammatory cytokines, chemokines and their receptors. Scanning electron microscopic analysis revealed demyelination characterized by myelin detachment from the axons in the early phase of EAE progression (days 3-7) in Klk6+/+ mice but not in Klk6-/- mice. Interestingly, anti-MOG (myelin oligodendrocyte glycoprotein) autoantibody was also detected in the cerebrospinal fluid (CSF) and spinal cord on day 3 after MOG immunization. Furthermore, treatment of primary cultured OLs with anti-MOG autoantibody induced oligoden...Continue Reading

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Citations

Jun 21, 2018·Biological Chemistry·Rahil EftekhariMorley D Hollenberg
Aug 24, 2018·Carcinogenesis·Nikolas KhouryGeorgia Sotiropoulou
Mar 27, 2019·Cells·John G Geisler
Apr 14, 2019·Molecular Oncology·Georgios PampalakisGeorgia Sotiropoulou
Nov 19, 2020·Nature Communications·Elisa M FloriddiaGonçalo Castelo-Branco
Oct 10, 2021·Glia·Hyesook YoonIsobel A Scarisbrick

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