期刊
BLOOD
卷 114, 期 15, 页码 3191-3198出版社
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2009-03-207522
关键词
-
类别
资金
- Juvenile Diabetes Research Foundation [1-2005-984]
- National Institutes of Health [AI066075]
- American Diabetes Association
Dendritic cells (DCs) play an instrumental role in regulating tolerance to self-antigens and preventing autoimmunity. One mechanism by which tolerogenic DCs are established is through the inhibitory effects of apoptotic cells (ACs). Immature DCs encountering ACs are resistant to stimuli that activate and mature DCs. We have shown that the Mer receptor tyrosine kinase (MerTK) plays a key role in transducing inhibitory signals upon binding of ACs, which in turn involve the phosphatidylinositol 3-kinase (PI3K) pathway. Nevertheless, the molecular basis for AC-induced inhibition of DCs is ill defined. In the current study, the proximal signaling events induced by MerTK after AC binding were studied. AC treatment of bone marrow-derived or splenic DCs established a complex consisting of MerTK, the nonreceptor tyrosine kinase c-Src, the transcription factor STAT3, and PI3K. In contrast, AC treatment of DCs lacking MerTK expression failed to increase c-Src and STAT3 activation. In addition, the inhibitory effects of ACs were blocked by treating DCs with pharmacologic inhibitors or siRNA specific for c-Src and STAT3. These findings demonstrate that AC-induced inhibition of DCs requires MerTK-dependent activation of c-Src and STAT3, and provide evidence for novel roles for c-Src and STAT3 in the immunoregulation of DCs. (Blood. 2009; 114: 3191-3198)
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