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Front. Immunol. | doi: 10.3389/fimmu.2018.00523

Astrocytic interleukin-15 reduces pathology of neuromyelitis optica in mice

Zhiguo Li1, 2,  Jinrui Han1,  Honglei Ren1, Cun-Gen Ma3, Fu-Dong Shi1, 2, 4, Qiang Liu1, 4 and  Minshu Li1, 2*
  • 1Neurology, Tianjin Institute of Neurology, China
  • 2Beijing Tiantan Hospital, Capital Medical University, China
  • 3Shanxi University of Traditional Chinese Medicine, China
  • 4Barrow Neurological Institute (BNI), United States

Astrocyte loss induced by NMO-IgG and complement-dependent cytotoxicity (CDC) is the hallmark of NMO pathology. The survival of astrocytes are 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, in which the expression of IL-15 is controlled by a glial fibrillary acidic protein (GFAP) promoter. We showed that astrocyte-targeted expression of IL-15 attenuates astrocytes and aquaporin 4 loss in the brain. Reduced BBB leakage and immune cells infiltration are also found in the lesion of IL-15tg mice subjected to NMO induction. In vitro data indicates that IL-15tg astrocytes are less susceptible to NMO-IgG-mediated CDC when compared to their WT littermates. Importantly, IL-15 enhances the ability of astrocyte to resistant to cytotoxicity and cell death via NF-кB signaling pathway. Our findings suggest that IL-15 reduces astrocyte loss and NMO pathology.

Keywords: Astrocytes, complement-dependent cytotoxicity, NMO-IgG, IL-15, Neuromyelitis Optica

Received: 11 Jan 2018; Accepted: 28 Feb 2018.

Edited by:

Antonio La Cava, University of California, Los Angeles, United States

Reviewed by:

Yinghong Hu, Emory University, United States
Nina Ivanovska, Institute of Microbiology (BAS), Bulgaria  

Copyright: © 2018 Li, Han, Ren, Ma, Shi, Liu and Li. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Minshu Li, Tianjin Institute of Neurology, Neurology, Tianjin, China,