期刊
MYASTHENIA GRAVIS AND RELATED DISORDERS: 11TH INTERNATIONAL CONFERENCE
卷 1132, 期 -, 页码 276-282出版社
WILEY-BLACKWELL
DOI: 10.1196/annals.1405.023
关键词
myasthenia gravis; experimental autoimmune myasthenia gravis; dendritic cells; regulatory T cells; GM-CSF; acetylcholine receptor
资金
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [R01AI058190] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE [K08NS058800] Funding Source: NIH RePORTER
- NIAID NIH HHS [R01 AI058190, R01 AI 058190-01] Funding Source: Medline
- NINDS NIH HHS [K08 NS058800, K08 NS058800-02] Funding Source: Medline
Current treatments for myasthenia gravis (MG) rely upon the administration of immunosuppressive agents which result in global, nonspecific attenuation of the immune response. An alternative approach would be to attempt to design therapies that specifically dampen autoreactivity without affecting general immunity. Recently, dendritic cells (DCs) have been shown to possess potent capabilities to tolerize T cells in an antigen-specific manner. We have observed that the selective activation of particular subsets of DCs utilizing granulocyte-macrophage colony-stimulating factor (GM-CSF) had profound effects on the induction of experimental autoimmune myasthenia gravis (EAMG). Specifically, treatment with GM-CSF effectively suppressed the induction of EAMG and down-modulated anti-AChR T cell and pathogenic antibody responses. These effects were associated with the activation of tolerogenic DCs, the enhanced production of suppressive cytokines, such as IL-10, and the mobilization of CD4(+)CD25(+) and FoxP3(+) regulatory T cells (Tregs). We have further shown that GM-CSF effectively ameliorates clinical disease severity in mice with active, ongoing EAMG. Based on these observations, we hypothesize that the selective activation of particular DC subsets in vivo using pharmacologic agents, like GM-CSF, can suppress ongoing anti-AChR immune responses by mobilizing antigen-specific Tregs capable of suppressing autoimmune MG.
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