CD8- DCs induce IL-12-independent Th1 differentiation through Delta 4 Notch-like ligand in response to bacterial LPS.

CD8- DCs induce IL-12-independent Th1 differentiation through Delta 4 Notch-like ligand in response to bacterial LPS.
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DOI:
10.1084/jem.20062305
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发表时间:
2007-07-09
期刊:
The Journal of experimental medicine
影响因子:
--
通讯作者:
Nussenzweig MC
Nussenzweig MC
中科院分区:
其他
文献类型:
--
作者:
Skokos D;Nussenzweig MC

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Toll样受体(Toll-like Receptor,TLR)通过诱导CD8+树突状细胞(DCs)分泌白介素12(IL-12),使T细胞向辅助性T细胞(Th)1分化。然而,依赖TLR的Th1反应在没有IL-12的情况下发生。为了确定DC在缺乏IL-12的情况下如何诱导Th1分化,我们检测了IL-12缺陷的DC对细菌脂多糖(LPS)的反应。我们发现,脂多糖通过CD8CD8CD8Th1型DC激活依赖于MyD88的Delta4Notch样配体的表达,并且这些细胞通过IL-12非依赖和Notch依赖的机制在体外和体内指导−的分化。因此,TLR4激活这两个DC亚群,通过两条不同的MyD88依赖的途径导致Th1反应。
Toll-like receptor (TLR) ligation is believed to skew T cell responses toward T helper (Th)1 differentiation by inducing interleukin (IL)-12 secretion by CD8+ dendritic cells (DCs). However, TLR-dependent Th1 responses occur in the absence of IL-12. To determine how DCs induce Th1 differentiation in the absence of IL-12, we examined the response of IL-12–deficient DCs to bacterial lipopolysaccharide (LPS). We find that LPS activates MyD88-dependent Delta 4 Notch-like ligand expression by CD8− DCs, and that these cells direct Th1 differentiation by an IL-12–independent and Notch-dependent mechanism in vitro and in vivo. Thus, activation of the two DC subsets by TLR4 leads to Th1 responses by two distinct MyD88-dependent pathways.
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影响因子: --
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