Interleukin-10 is a critical regulator of white matter lesion containment following viral induced demyelination (MUC2P.940)

Formation of the astroglial scar in response to CNS injury is essential in limiting inflammation and damage to defined areas and initiating repair.The universal nature of this response suggests that defining mechanisms by which astrocytes segregate areas of tissue injury and promote repair is fundamental to confining demyelination.Neurotropic coronavirus induces an acute encephalomyelitis along with focal demyelination in which the initial lesions only increase slightly after the control of infection.Focal lesions are characterized by axonal sparing, myelin ingestion by microglia,and glial scars associated with hypertrophic astrocytes.Virus control is accelerated in mice lacking anti-inflammatory IL-10 resulting in limited initial demyelination.Despite ongoing viral control lesions fail to be confined and show sustained expansion providing a model of dysregulated white matter injury temporally remote from the acute CNS insult.Expanding IL-10-/- lesions are characterized by sustained microglial activation, partial loss of deactivated microglia and a lack of galectin-1 expressing astrocytes.Although IL-10 deficiency does not prevent astrocyte hypertrophy, astrocyte organization into mesh like structures at lesion borders is impaired. Formation of discrete foci of demyelination correlated with IL-10Rα expression on astrocytes in lesioned areas, highlighting a critical role for IL-10 signaling to astrocytes in limiting the expansion of the initial lesions into adjacent areas.