IL-33-activated dendritic cells induce an atypical TH2-type response.

IL-33-activated dendritic cells induce an atypical TH2-type response.
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DOI:
10.1016/j.jaci.2009.02.026
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发表时间:
2009-05
影响因子:
14.2
通讯作者:
Kita, Hirohito
Kita, Hirohito
中科院分区:
医学1区
文献类型:
--
作者:
Rank, Matthew A.;Kobayashi, Takao;Kozaki, Hideaki;Barternes, Kathleen R.;Squillace, Diane L.;Kita, Hirohito

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IL-33是最近发现的IL-1家族细胞因子,参与体内th2型反应的发展。然而,我们对IL-33的细胞靶点知之甚少。我们测试了树突状细胞(dc)响应IL-33和IL-33激活dc prime naïve CD4+ T细胞产生th2型细胞因子的假设。dc来源于小鼠骨髓,通过流式细胞术和实时RT-PCR检测其IL-33受体ST2的表达。通过FACS (MHC II和CD86的表达)和ELISA (IL-6和IL-12的产生)检测DCs对IL-33的反应。通过与分离的CD4+ T细胞共培养和测量上清液中的细胞因子,评估il -33活化的dc对naïve T细胞的诱导能力。在高纯化的dc中检测到ST2 mRNA。ST2蛋白在树突状细胞中含量丰富,但在细胞表面几乎检测不到。与IL-33孵育的DCs增加了MHC II和CD86的表达和IL-6的产生,但没有产生IL-12。抗st2抗体抑制il -33活化的dc产生IL-6约60%;抗st2不影响lps激活的dc产生IL-6。当与naïve CD4+ T细胞单独孵育时,IL-33不能刺激细胞因子的产生。相比之下,naïve CD4+ T细胞与il -33激活的dc孵育显示IL-5和IL-13的强劲生产,但IL-4和IFN-γ检测不到。dc通过ST2直接响应IL-33。IL-33和DC相互作用可能是启动th2型免疫应答的新途径。
IL-33, a recently discovered IL-1 family cytokine, is implicated in the development of Th2-type responses in vivo. However, the cellular target(s) for IL-33 are poorly understood. We tested the hypotheses that dendritic cells (DCs) respond to IL-33 and that IL-33-activated DCs prime naïve CD4+ T cells to produce Th2-type cytokines. DCs were derived from mouse bone marrow, and their expression of the IL-33 receptor, ST2, was examined by FACS and real-time RT-PCR. The DCs’ responses to IL-33 were examined by FACS (MHC II and CD86 expression) and by ELISA (IL-6 and IL-12 production). The ability of IL-33-activated DCs to prime naïve T cells was assessed by coculture with isolated CD4+ T cells and by measuring cytokines in the supernatants. ST2 mRNA was detectable in highly purified DCs. ST2 protein was abundant within DCs, but was barely detectable on their cell surface. Incubation of DCs with IL-33 increased their expression of MHC II and CD86 and production of IL-6, but IL-12 was not produced. Anti-ST2 antibody inhibited IL-6 production from IL-33-activated DCs by approximately 60%; anti-ST2 did not affect IL-6 production from LPS-activated DCs. When incubated with naïve CD4+ T cells alone, IL-33 failed to stimulate cytokine production. In contrast, naïve CD4+ T cells incubated with IL-33-activated DCs showed robust production of IL-5 and IL-13, but IL-4 and IFN-γ were undetectable. DCs respond directly to IL-33 through ST2. The IL-33 and DC interaction may represent a new pathway to initiate Th2-type immune responses.
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