B cell activating factor is central to bleomycin- and IL-17-mediated experimental pulmonary fibrosis
B cell activating factor is central to bleomycin- and IL-17-mediated experimental pulmonary fibrosis
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DOI：
10.1016/j.jaut.2014.08.003
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发表时间：
2015-01-01
影响因子：
12.8
通讯作者：
Couillin, Isabelle
中科院分区：
文献类型：
--
作者：
Francois, Antoine;Gombault, Aurelie;Couillin, Isabelle
特发性肺纤维化（IPF）是一种病因不明的进行性破坏性纤维化疾病。我们研究了b细胞活化因子（BAFF）的作用，BAFF是TNF家族成员，最近涉及自身免疫性疾病中致病性il -17产生细胞的调节。在博来霉素诱导的小鼠肺纤维化模型中评估了BAFF的作用。我们发现，在博来霉素暴露后，小鼠支气管肺泡间隙和肺部的BAFF水平明显升高。我们发现Gr1（+）中性粒细胞是blm诱导的肺部炎症和纤维化的重要来源。BAFF基因消融或BAFF可溶性受体中和可显著减轻肺纤维化和IL-1 β水平。我们进一步证明，博莱霉素诱导的BAFF表达和肺纤维化依赖于IL-1 β和IL-17A。BAFF是IL-17A诱导的肺纤维化和体外小鼠纤维化肺中CD3(+) T细胞增加IL-17A产生所必需的。最后，我们报告IPF患者支气管肺泡灌洗液中BAFF水平升高。因此，我们的数据支持BAFF在肺纤维化的建立中的作用，以及IL-1 β、BAFF和IL-17A之间的串扰。(C) 2014 Elsevier Ltd.版权所有。
Idiopathic pulmonary fibrosis (IPF) is a progressive devastating, yet untreatable fibrotic disease of unknown origin. We investigated the contribution of the B-cell activating factor (BAFF), a TNF family member recently implicated in the regulation of pathogenic IL-17-producing cells in autoimmune diseases. The contribution of BAFF was assessed in a murine model of lung fibrosis induced by airway administered bleomycin. We show that murine BAFF levels were strongly increased in the bronchoalveolar space and lungs after bleomycin exposure. We identified Gr1(+) neutrophils as an important source of BAFF upon BLM-induced lung inflammation and fibrosis. Genetic ablation of BAFF or BAFF neutralization by a soluble receptor significantly attenuated pulmonary fibrosis and IL-1 beta levels. We further demonstrate that bleomycin-induced BAFF expression and lung fibrosis were IL-1 beta and IL-17A dependent. BAFF was required for rIL-17A-induced lung fibrosis and augmented IL-17A production by CD3(+) T cells from murine fibrotic lungs ex vivo. Finally we report elevated levels of BAFF in bronchoalveolar lavages from IPF patients. Our data therefore support a role for BAFF in the establishment of pulmonary fibrosis and a crosstalk between IL-1 beta, BAFF and IL-17A. (C) 2014 Elsevier Ltd. All rights reserved.