期刊
CLINICAL AND EXPERIMENTAL IMMUNOLOGY
卷 170, 期 3, 页码 254-265出版社
WILEY
DOI: 10.1111/j.1365-2249.2012.04661.x
关键词
astrocyte; experimental autoimmune encephalitomyelitis; IL-27; MHC-II; multiple sclerosis
类别
资金
- Master Innovation Research Foundation of Hei Longjiang Province [YJSCX2011-325HLJ]
- Natural Science Foundation for Youth of China [30901330, 81000512, 81100883]
- Natural Science Foundation of China [81171121]
- Doctoral Fund of the Ministry of Education of China [20102307110013]
- Open project of key laboratory of Myocardical Ischemia Mechanism and Treatment [KF201013]
The nature of pathogenic mechanisms associated with the development of multiple sclerosis (MS) have long been debated. However, limited research was conducted to define the interplay between infiltrating lymphocytes and resident cells of the central nervous system (CNS). Data presented in this report describe a novel role for astrocyte-mediated alterations to myelin oligodendrocyte glycoprotein (MOG)(35-55)-specific lymphocyte responses, elicited during the development of experimental autoimmune encephalitomyelitis (EAE). In-vitro studies demonstrated that astrocytes inhibited the proliferation and interferon (IFN)-gamma, interleukin (IL)-4, IL-17 and transforming growth factor (TGF)-beta secretion levels of MOG(35-55)-specific lymphocytes, an effect that could be ameliorated by astrocyte IL-27 neutralization. However, when astrocytes were pretreated with IFN-gamma, they could promote the proliferation and secretion levels of MOG(35-55)-specific lymphocytes, coinciding with apparent expression of major histocompatibility complex (MHC)-II on astrocytes themselves. Quantitative polymerase chain reaction (qPCR) demonstrated that production of IL-27 in the spinal cord was at its highest during the initial phases. Conversely, production of IFN-gamma in the spinal cord was highest during the peak phase. Quantitative analysis of MHC-II expression in the spinal cord showed that there was a positive correlation between MHC-II expression and IFN-gamma production. In addition, astrocyte MHC-II expression levels correlated positively with IFN-gamma production in the spinal cord. These findings suggested that astrocytes might function as both inhibitors and promoters of EAE. Astrocytes prevented MOG(35-55)-specific lymphocyte function by secreting IL-27 during the initial phases of EAE. Then, in the presence of higher IFN-gamma levels in the spinal cord, astrocytes were converted into antigen-presenting cells. This conversion might promote the progression of pathological damage and result in a peak of EAE severity.
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