期刊
JOURNAL OF IMMUNOLOGY
卷 188, 期 7, 页码 3107-3115出版社
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.1103308
关键词
-
类别
资金
- National Institutes of Health [AR056296]
- American Lebanese Syrian Associated Charities
Recent findings have demonstrated an indispensable role for GM-CSF in the pathogenesis of experimental autoimmune encephalomyelitis. However, the signaling pathways and cell populations that regulate GM-CSF production in vivo remain to be elucidated. Our work demonstrates that IL-1R is required for GM-CSF production after both TCR- and cytokine-induced stimulation of immune cells in vitro. Conventional alpha beta and gamma delta T cells were both identified to be potent producers of GM-CSF. Moreover, secretion of GM-CSF was dependent on IL-1R under both IL-12- and IL-23-induced stimulatory conditions. Deficiency in IL-1R conferred significant protection from experimental autoimmune encephalomyelitis, and this correlated with reduced production of GM-CSF and attenuated infiltration of inflammatory cells into the CNS. We also find that GM-CSF production in vivo is not restricted to a defined CD4(+) T cell lineage but is rather heterogeneously expressed in the effector CD4(+) T cell population. In addition, inflammasome-derived IL-1 beta upstream of IL-1R is a critical regulator of GM-CSF production by T cells during priming, and the adapter protein, MyD88, promotes GM-CSF production in both alpha beta and gamma delta T cells. These findings highlight the importance of inflammasome-derived IL-1 beta and the IL-1R/MyD88 signaling axis in the regulation of GM-CSF production. The Journal of Immunology, 2012, 188: 3107-3115.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据