IL-4-Producing Dendritic Cells Induced during Schistosoma japonica Infection Promote Th2 Cells via IL-4-Dependent Pathway

IL-4-Producing Dendritic Cells Induced during Schistosoma japonica Infection Promote Th2 Cells via IL-4-Dependent Pathway
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DOI:
10.4049/jimmunol.1403240
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发表时间:
2015-10-15
影响因子:
4.4
通讯作者:
Chen, Xiao-Ping
Chen, Xiao-Ping
中科院分区:
医学2区
文献类型:
--
作者:
Ma, Yi-Lei;Huang, Feng-Juan;Chen, Xiao-Ping

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尽管树突状细胞(dc)已被广泛证明在蠕虫感染和过敏反应中启动Th2反应中发挥重要作用,但其机制仍不确定,主要是因为dc不产生IL-4。在目前的研究中,我们发现了一个新的dc亚群,来自感染了Th2引发病原体日本血吸虫的小鼠,它通过il -4依赖途径独立地促进Th2细胞。与嗜碱性细胞相比,这些dc含有相似水平的IL-4 mRNA和更高水平的IL-12p40 mRNA,这与它们促进th2和th1的双极化能力有关。以Fc ε - RI+的表达为特征,这些dc是独立于T细胞诱导的。进一步研究发现,促进Th2的Fc epsilon RI+ dc是单核细胞来源的炎性dc,足以在体内诱导Th2细胞。卵Ags联合GM-CSF或单独IL-3能够在体外刺激骨髓细胞生成促th2的Fc epsilon RI+ DCs。据我们所知,我们的数据首次表明,产生il -4的dc在一些Th2激发的情况下被诱导,它们应该在Th2应答的启动中发挥重要作用。
Although dendritic cells (DCs) have been widely demonstrated to play essential roles in initiation of Th2 responses in helminth infections and allergic reactions, the mechanisms remain uncertain largely because DCs do not produce IL-4. In present investigation, we have uncovered a novel subset of DCs from mice infected with Th2-provoking pathogens Schistosoma japonica, which independently promoted Th2 cells via IL-4-dependent pathway. These DCs contained similar levels of IL-4 mRNA and higher levels of IL-12p40 mRNA comparing to basophils, correlating to their Th2-promoting and Th1-promoting dual polarization capacities. Characterized by expression of Fc epsilon RI+, these DCs were induced independent of T cells. Further investigations revealed that Th2-promoting Fc epsilon RI+ DCs were monocyte-derived inflammatory DCs, which were sufficient to induce Th2 cells in vivo. Egg Ags together with GM-CSF or IL-3 alone were able to stimulate the generation of Th2-promoting Fc epsilon RI+ DCs from bone marrow cells in vitro. To our knowledge, our data for the first time demonstrate that IL-4-producing DCs are induced under some Th2-provoking situations, and they should play important roles in initiation of Th2 response.