Department of Allergy and Clinical Immunology and.
Int Immunol. 2014 Feb;26(2):103-14. doi: 10.1093/intimm/dxt047. Epub 2013 Oct 22.
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.
树突状细胞 (DCs) 在决定 CD4⁺ T 细胞的命运方面发挥着关键作用。在 DC 亚群中，已证明单核细胞衍生的炎性 DCs (iDCs) 在炎症条件下诱导适应性免疫反应中发挥重要作用。尽管先前的研究表明，DCs 在小鼠哮喘模型中诱导过敏气道炎症和气道高反应性 (AHR) 中具有不可或缺的作用，但 iDCs 在哮喘反应中的确切作用在很大程度上仍不清楚。我们在这里表明，T(h)2 细胞介导的炎症在小鼠哮喘模型中诱导 iDCs 表达一些替代性激活巨噬细胞的标志物，如精氨酸酶 1 和抵抗素样分子-α，其机制依赖于 STAT6 的内在表达。相比之下，T(h)1 细胞介导的炎症诱导 iDCs 表达 TNF-α 和诱导型一氧化氮合酶 (iNOS)，这是 TNF-α 和 iNOS 产生 DCs 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，与过敏气道炎症无关。因此，我们的研究结果表明，iDCs 在 T(h)2 细胞介导的哮喘反应中作为下游效应细胞诱导 AHR 方面具有重要意义。
