IL-33 Amplifies the Polarization of Alternatively Activated Macrophages That Contribute to Airway Inflammation
IL-33 Amplifies the Polarization of Alternatively Activated Macrophages That Contribute to Airway Inflammation
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DOI：
10.4049/jimmunol.0901575
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发表时间：
2009-11-15
影响因子：
4.4
通讯作者：
Liew, Foo Y.
中科院分区：
文献类型：
--
作者：
Kurowska-Stolarska, Mariola;Stolarski, Bartosz;Liew, Foo Y.
选择性活化的巨噬细胞（AAM）在2型免疫中起关键作用。缺乏ST2（白细胞介素 - 1家族最新成员白细胞介素 - 33的受体）的小鼠具有受损的2型免疫应答。因此我们推断白细胞介素 - 33/ST2信号可能参与气道炎症期间AAM的分化和活化。我们在此报道，在白细胞介素 - 33诱导的气道炎症期间，白细胞介素 - 33以白细胞介素 - 13依赖的方式将肺泡巨噬细胞的静止表型转变为表达甘露糖受体、白细胞介素 - 4Rα并产生高水平的CCL24和CCL17的AAM表型。中和AAM衍生的CCL24可改善白细胞介素 - 33诱导的肺部嗜酸性粒细胞增多。此外，肺泡巨噬细胞的耗竭减少了白细胞介素 - 33诱导的气道炎症。另外，ST2（-/-）小鼠中OVA诱导的气道炎症减弱与AAM分化减少有关。在体外，白细胞介素 - 33通过增加精氨酸酶1、Ym1的表达以及CCL24和CCL17的产生，放大白细胞介素 - 13诱导的肺泡巨噬细胞和骨髓来源巨噬细胞向AAM表型的极化。白细胞介素 - 13/白细胞介素 - 4Rα信号通过诱导ST2L的表达对白细胞介素 - 33驱动的AAM扩增至关重要。最后，我们表明白细胞介素 - 33在哮喘患者的肺上皮细胞中比健康对照者表达更丰富，这表明白细胞介素 - 33可能参与临床哮喘中肺巨噬细胞的活化。综上所述，我们在此证明白细胞介素 - 33/ST2在AAM极化的扩增和趋化因子产生中起重要作用，这有助于先天性和抗原诱导的气道炎症。《免疫学杂志》，2009年，183卷：6469 - 6477页。
Alternatively activated macrophages (AAM) play a crucial role in type 2 immunity. Mice deficient in ST2, a receptor for the latest member of the IL-1 family, IL-33, have impaired type 2 immune responses. We therefore reasoned that IL-33/ST2 signaling may be involved in the differentiation and activation of AAM during airway inflammation. We report here that IL-33 changed the quiescent phenotype of alveolar macrophages toward an AAM phenotype that expressed mannose receptor, IL-4R alpha, and produced high levels of CCL24 and CCL17 in an IL-13-dependent manner during IL-33-induced airway inflammation. Neutralization of AAM-derived CCL24 led to an amelioration of IL-33-induced eosinophilia in the lungs. Moreover, depletion of alveolar macrophages reduced IL-33-induced airway inflammation. Additionally, the attenuated OVA-induced airway inflammation in ST2(-/-) mice was associated with a decrease in AAM differentiation. In vitro, IL-33 amplified IL-13-induced polarization of alveolar- and bone marrow-derived macrophage toward an AAM phenotype by increasing the expression of arginase 1, Ym1, as well as the production of CCL24 and CCL17. IL-13/IL-4R alpha signaling was crucial for IL-33-driven AAM amplification by inducing the expression of ST2L. Finally, we showed that IL-33 was more abundantly expressed in the lung epithelial cells of asthma patients than those from healthy controls, suggesting that IL-33 may be involved in lung macrophage activation in clinical asthma. Taken together, we demonstrate here that IL-33/ST2 plays a significant role in the amplification of AAM polarization and chemokine production which contribute to innate and Ag-induced airway inflammation. The Journal of Immunology, 2009,183: 6469-6477.