Department
neurobiology
Document Type
Article
Abstract
Astrocyte loss induced by neuromyelitis optica (NMO)-IgG and complement-dependent cytotoxicity (CDC) is the hallmark of NMO pathology. The survival of astrocytes is thought to reflect astrocyte exposure to environmental factors in the CNS and the response of astrocytes to these factors. However, still unclear are how astrocytes respond to NMO-IgG and CDC, and what CNS environmental factors may impact the survival of astrocytes. In a murine model of NMO induced by intracerebral injection of NMO-IgG and human complement, we found dramatic upregulation of IL-15 in astrocytes. To study the role of astrocytic IL-15 in NMO, we generated a transgenic mouse line with targeted expression of IL-15 in astrocytes (IL-15tg), in which the expression of IL-15 is controlled by a glial fibrillary acidic protein promoter. We showed that astrocyte-targeted expression of IL-15 attenuates astrocyte injury and the loss of aquaporin-4 in the brain. Reduced blood-brain barrier leakage and immune cell infiltration are also found in the lesion of IL-15tg mice subjected to NMO induction. IL-15tg astrocytes are less susceptible to NMO-IgG-mediated CDC than their wild-type counterparts. The enhanced resistance of IL-15tg astrocytes to cytotoxicity and cell death involves NF-κB signaling pathway. Our findings suggest that IL-15 reduces astrocyte loss and NMO pathology.
Publication Date
3-19-2018
Publication Title
Frontiers in Immunology
ISSN
16643224
Volume
9
Digital Object Identifier (DOI)
10.3389/fimmu.2018.00523
Recommended Citation
Li, Zhiguo; Han, Jinrui; Ren, Honglei; Ma, Cun Gen; Shi, Fu Dong; Liu, Qiang; and Li, Minshu, "Astrocytic Interleukin-15 Reduces Pathology Of Neuromyelitis Optica In Mice" (2018). Translational Neuroscience. 126.
https://scholar.barrowneuro.org/neurobiology/126