Th2-type inflammation instructs inflammatory dendritic cells to induce airway hyperreactivity.
Th2-type inflammation instructs inflammatory dendritic cells to induce airway hyperreactivity.
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DOI：
10.1093/intimm/dxt047
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发表时间：
2014-02
影响因子：
4.4
通讯作者：
A. Iwata;Saki Kawashima;Midori Kobayashi;A. Okubo;Hirotoshi Kawashima;A. Suto;K. Hirose;T. Nakayama;H. Nakajima
中科院分区：
文献类型：
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作者：
A. Iwata;Saki Kawashima;Midori Kobayashi;A. Okubo;Hirotoshi Kawashima;A. Suto;K. Hirose;T. Nakayama;H. Nakajima
树突状细胞（Dendritic cells，DC）在决定CD 4 + T细胞的命运中起关键作用。在DC亚群中，单核细胞衍生的炎性DC（iDC）已显示在炎症条件下诱导适应性免疫应答中起重要作用。尽管先前的研究表明，DC在小鼠哮喘模型中诱导过敏性气道炎症和气道高反应性（AHR）中具有不可或缺的作用，但iDC在哮喘反应中的确切作用在很大程度上仍然未知。我们发现T（h）2细胞介导的哮喘小鼠模型中的炎症通过依赖于STAT 6的内在表达的机制诱导iDC中的一些交替活化的巨噬细胞标志物的表达，例如活化酶1和抵抗素样分子-α。相反，T（h）1细胞介导的炎症诱导iDC表达TNF-α和诱导型一氧化氮合酶（iNOS），它们是产生TNF-α和iNOS的DC的标志物。此外，我们表明，在T（h）2环境下的iDCs在诱导AHR中发挥重要作用，独立于过敏性气道炎症。因此，我们的研究结果表明，在T（h）2细胞介导的哮喘反应中，iDC作为下游效应细胞在诱导AHR中的重要性。
Dendritic cells (DCs) play critical roles in determining the fate of CD4⁺ T cells. Among DC sub-populations, monocyte-derived inflammatory DCs (iDCs) have been shown to play an important role in the induction of adaptive immune responses under inflammatory conditions. Although previous studies have shown that DCs have an indispensable role in the induction of allergic airway inflammation and airway hyperreactivity (AHR) in murine asthma models, the precise roles of iDCs in the asthmatic responses remain largely unknown. We show here that T(h)2 cell-mediated inflammation in murine asthma models induces the expression of some markers of alternatively activated macrophage such as arginase 1 and resistin-like molecule-α in iDCs by a mechanism depending on the intrinsic expression of STAT6. In contrast, T(h)1 cell-mediated inflammation induces iDCs to express TNF-α and inducible nitric oxide synthase (iNOS), markers of TNF-α- and iNOS-producing DCs. Moreover, we show that iDCs under a T(h)2 environment play an important role in the induction of AHR, independently of allergic airway inflammation. Our results thus indicate the importance of iDCs in the induction of AHR as downstream effector cells in T(h)2 cell-mediated asthmatic responses.