期刊
BLOOD
卷 115, 期 6, 页码 1156-1165出版社
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2009-07-235382
关键词
-
类别
资金
- Deutsche Forschungsgemeinschaft (DFG
- German Research Foundation)
- Ministry of Science, Research
- Arts Baden-Wurttemberg
- European Social Fund (ESF)
- Deutsche Jose Carreras Leukamie-Stiftung eV
- Deutscher Akademischer Austauschdienst (DAAD
- German Academic Exchange Service)
- US Public Health Service [P50 CA97274]
Human plasmacytoid dendritic cells (pDCs) are crucially involved in the modulation of adaptive T-cell responses in the course of neoplastic, viral, and autoimmune disorders. In several of these diseases elevated extracellular levels of the serine protease granzyme B (GrB) are observed. Here we demonstrate that human pDCs can be an abundant source of GrB and that such GrB(+) pDCs potently suppress T-cell proliferation in a GrB-dependent, perforin-independent manner, a process reminiscent of regulatory T cells. Moreover, we show that GrB expression is strictly regulated on a transcriptional level involving Janus kinase 1 (JAK1), signal transducer and activator of transcription 3 (STAT3), and STAT5 and that interleukin-3 (IL-3), a cytokine secreted by activated T cells, plays a central role for GrB induction. Moreover, we find that the immunosuppressive cytokine IL-10 enhances, while Toll-like receptor agonists and CD40 ligand strongly inhibit, GrB secretion by pDCs. GrB-secreting pDCs may play a regulatory role for immune evasion of tumors, antiviral immune responses, and autoimmune processes. Our results provide novel information about the complex network of pDC-T-cell interactions and may contribute to an improvement of prophylactic and therapeutic vaccinations. (Blood. 2010;115:1156-1165)
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