IL-33 promotes DC development in BM culture by triggering GM-CSF production.

IL-33 promotes DC development in BM culture by triggering GM-CSF production.
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DOI:
10.1002/eji.200939472
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发表时间:
2009-12
影响因子:
5.4
通讯作者:
Takashima, Akira
Takashima, Akira
中科院分区:
医学3区
文献类型:
--
作者:
Mayuzumi, Nobuyasu;Matsushima, Hironori;Takashima, Akira

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用GM-CSF和其他细胞因子产生的短期DC培养物显著提高了我们研究DC免疫生物学的能力。在这里,我们分别测试了65种细胞因子在小鼠BM培养系统中促进CD 11 c+细胞生成的潜力。除了已知促进DC存活和/或生长的几种细胞因子之外,发现IL-33以时间和剂量依赖性方式增加DC发育。尽管在IL-33存在下产生的所得CD 11 c+细胞表现出典型的树突状形态,但它们仅以适度水平表达MHC II类分子,对TLR配体的反应可忽略不计,不产生可检测的IL-12 p70,在表面上展示PD-L1和PD-L2,并且未能有效激活免疫幼稚T细胞。IL-33诱导的CD 11 c+细胞的扩增被抗GM-CSF mAb完全阻断,并且加入IL-33后BM培养中GM-CSF mRNA和蛋白表达显著升高,表明IL-33通过GM-CSF依赖性方式间接促进体外DC生成。关于细胞来源,仅在CD 45 +/FcεRI+ BM群体中观察到IL-33依赖性GM-CSF产生。我们的研究结果不仅加强了GM-CSF作为主要DC生长因子的概念,还揭示了以前未被认识到的支持DC发育的机制。
Short-term DC cultures generated with GM-CSF and other cytokines have markedly improved our ability to study the immunobiology of DC. Here we tested 65 cytokines individually for their potentials to promote generation of CD11c+ cells in a murine BM culture system. In addition to several cytokines known to promote DC survival and/or growth, IL-33 was found to augment DC development time- and dose-dependently. Although the resulting CD11c+ cells generated in the presence of IL-33 exhibited a typical dendritic morphology, they expressed MHC class II molecules only at modest levels, showed negligible responses to TLR ligands, produced no detectable IL-12 p70, displayed PD-L1 and PD-L2 on the surface, and failed to activate immunologically naïve T cells efficiently. IL-33-induced expansion of CD11c+ cells was completely blocked by anti-GM-CSF mAb, and GM-CSF mRNA and protein expression in BM culture was markedly elevated by added IL-33, indicating that IL-33 promotes in vitro DC generation indirectly by a GM-CSF-dependent manner. With regard to the cellular source, IL-33-dependent GM-CSF production was observed exclusively within the CD45+/FcεRI+ BM population. Not only do our results reinforce the notion that GM-CSF serves as a primary DC growth factor, they also reveal a previously unrecognized mechanism supporting DC development.
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