IL-33 promotes ST2-dependent lung fibrosis by the induction of alternatively activated macrophages and innate lymphoid cells in mice.
IL-33 promotes ST2-dependent lung fibrosis by the induction of alternatively activated macrophages and innate lymphoid cells in mice.
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DOI：
10.1016/j.jaci.2014.05.011
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发表时间：
2014-12
影响因子：
14.2
通讯作者：
Xu, Damo
中科院分区：
文献类型：
--
作者：
Li, Dong;Guabiraba, Rodrigo;Besnard, Anne-Gaelle;Komai-Koma, Mousa;Jabir, Majid S.;Zhang, Li;Graham, Gerard J.;Kurowska-Stolarska, Mariola;Liew, Foo Y.;McSharry, Charles;Xu, Damo
肺纤维化的发生和调控机制尚不清楚。IL-33是呼吸系统疾病的重要细胞因子，在特发性肺纤维化患者的肺中过表达。我们的目的是确定IL-33对博莱霉素诱导的小鼠肺纤维化的发展和严重程度的影响和机制。在用重组成熟形式的IL-33或抗IL-33抗体处理或用2型先天淋巴样细胞（ILC 2）转移的野生型或Il 33 r（St 2）−/− C57 BL/6小鼠中，博莱霉素诱导肺纤维化。根据肺组织学、胶原水平和灌洗液细胞学评价纤维化的发展和严重程度。通过使用定量PCR、ELISA和细胞计量术定量细胞因子和趋化因子水平。IL-33在肺上皮细胞中组成型表达，但在巨噬细胞中由博来霉素诱导。博莱霉素增强了肺组织中成熟但减少的全长形式的IL-33的产生。ST 2缺陷、抗IL-33抗体治疗或肺泡巨噬细胞耗竭减弱和外源性IL-33或ILC 2过继转移增强博来霉素诱导的肺部炎症和纤维化。这些病理变化分别伴随着肺中IL-33、IL-13、TGF-β1和炎性趋化因子产生的减少或增加。此外，IL-33极化M2巨噬细胞产生IL-13和TGF-β1，并诱导ILC 2扩增产生IL-13。IL-33是一种新的促纤维化细胞因子，其通过ST 2发出信号，以ST 2和巨噬细胞依赖性方式通过募集和引导炎性细胞功能并增强促纤维化细胞因子产生来促进肺纤维化的起始和进展。
The initiation and regulation of pulmonary fibrosis are not well understood. IL-33, an important cytokine for respiratory diseases, is overexpressed in the lungs of patients with idiopathic pulmonary fibrosis. We aimed to determine the effects and mechanism of IL-33 on the development and severity of pulmonary fibrosis in murine bleomycin-induced fibrosis. Lung fibrosis was induced by bleomycin in wild-type or Il33r (St2)−/− C57BL/6 mice treated with the recombinant mature form of IL-33 or anti–IL-33 antibody or transferred with type 2 innate lymphoid cells (ILC2s). The development and severity of fibrosis was evaluated based on lung histology, collagen levels, and lavage cytology. Cytokine and chemokine levels were quantified by using quantitative PCR, ELISA, and cytometry. IL-33 is constitutively expressed in lung epithelial cells but is induced in macrophages by bleomycin. Bleomycin enhanced the production of the mature but reduced full-length form of IL-33 in lung tissue. ST2 deficiency, anti–IL-33 antibody treatment, or alveolar macrophage depletion attenuated and exogenous IL-33 or adoptive transfer of ILC2s enhanced bleomycin-induced lung inflammation and fibrosis. These pathologic changes were accompanied, respectively, by reduced or increased IL-33, IL-13, TGF-β1, and inflammatory chemokine production in the lung. Furthermore, IL-33 polarized M2 macrophages to produce IL-13 and TGF-β1 and induced the expansion of ILC2s to produce IL-13 in vitro and in vivo. IL-33 is a novel profibrogenic cytokine that signals through ST2 to promote the initiation and progression of pulmonary fibrosis by recruiting and directing inflammatory cell function and enhancing profibrogenic cytokine production in an ST2- and macrophage-dependent manner.
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影响因子：
4.4
作者：
Kurowska-Stolarska, Mariola;Kewin, Pete;Xu, Damo
通讯作者：
Xu, Damo
影响因子：
4.4
作者：
Kurowska-Stolarska, Mariola;Stolarski, Bartosz;Liew, Foo Y.
通讯作者：
Liew, Foo Y.
DOI：
10.1084/jem.20121964
发表时间：
2013-03-11
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Molofsky AB;Nussbaum JC;Liang HE;Van Dyken SJ;Cheng LE;Mohapatra A;Chawla A;Locksley RM
通讯作者：
Locksley RM
DOI：
10.1165/rcmb.2008-0182oc
发表时间：
2009-12
影响因子：
6.4
作者：
通讯作者：
--
影响因子：
64.8
作者：
通讯作者：
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