title: Interleukin-10 is a critical regulator of white matter lesion containment following viral induced demyelination.
abstract: Neurotropic coronavirus induces an acute encephalomyelitis accompanied by focal areas of demyelination distributed randomly along the spinal column. The initial areas of demyelination increase only slightly after the control of infection. These circumscribed focal lesions are characterized by axonal sparing, myelin ingestion by macrophage/microglia, and glial scars associated with hypertrophic astrocytes, which proliferate at the lesion border. Accelerated virus control in mice lacking the anti-inflammatory cytokine IL-10 was associated with limited initial demyelination, but low viral mRNA persistence similar to WT mice and declining antiviral cellular immunity. Nevertheless, lesions exhibited sustained expansion providing a model of dysregulated white matter injury temporally remote from the acute CNS insult. Expanding lesions in the absence of IL-10 are characterized by sustained microglial activation and partial loss of macrophage/microglia exhibiting an acquired deactivation phenotype. Furthermore, IL-10 deficiency impaired astrocyte organization into mesh like structures at the lesion borders, but did not prevent astrocyte hypertrophy. The formation of discrete foci of demyelination in IL-10 sufficient mice correlated with IL-10 receptor expression exclusively on astrocytes in areas of demyelination suggesting a critical role for IL-10 signaling to astrocytes in limiting expansion of initial areas of white matter damage. GLIA 2015;63:2106-2120.
authors.affiliation: Department of Neurosciences, Lerner Research Institute, The Cleveland Clinic, Cleveland, Ohio.
authors.forename: Shweta S
authors.initials: SS
authors.lastname: Puntambekar
authors.affiliation: Department of Pathology, The University of Southern California Keck School of Medicine, Los Angeles, California.
authors.forename: David R
authors.initials: DR
authors.lastname: Hinton
authors.affiliation: Department of Neurosciences, Lerner Research Institute, The Cleveland Clinic, Cleveland, Ohio.
authors.forename: Xinghua
authors.initials: X
authors.lastname: Yin
authors.affiliation: Department of Neurosciences, Lerner Research Institute, The Cleveland Clinic, Cleveland, Ohio.
authors.forename: Carine
authors.initials: C
authors.lastname: Savarin
authors.affiliation: Department of Neurosciences, Lerner Research Institute, The Cleveland Clinic, Cleveland, Ohio.
authors.forename: Cornelia C
authors.initials: CC
authors.lastname: Bergmann
authors.affiliation: Department of Neurosciences, Lerner Research Institute, The Cleveland Clinic, Cleveland, Ohio.
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Trapp
authors.affiliation: Department of Neurosciences, Lerner Research Institute, The Cleveland Clinic, Cleveland, Ohio.
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Stohlman
keywords: astrocyte; demyelination; interleukin-10; microglia; virus