A Role for Dendritic Cells in Bleomycin-induced Pulmonary Fibrosis in Mice?
A Role for Dendritic Cells in Bleomycin-induced Pulmonary Fibrosis in Mice?
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DOI：
10.1164/rccm.200907-1164oc
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发表时间：
2010-08-01
影响因子：
24.7
通讯作者：
Soler, Paul
中科院分区：
文献类型：
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作者：
Bantsimba-Malanda, Claudie;Marchal-Somme, Joelle;Soler, Paul
肺树突状细胞（DCs）在人纤维化肺疾病中有大量的积累，但DCs在肺纤维化发病机制中的作用尚不清楚。目的：在博来霉素诱导的小鼠肺纤维化的体内模型中研究肺DCs的特征。我们通过流式细胞术对肺单个核细胞进行了流式细胞术，以表征博莱霉素诱导的肺损伤过程中肺DCs的动力学和活化。细胞悬液我们还表征了在博来霉素肺中积聚的淋巴细胞和易于促进免疫细胞募集的趋化因子。测量和主要结果：我们首次发现，CD 11 c（+）/主要组织相容性复合物II类+DC数量的增加，包括CD 11b（hl）单核细胞衍生的炎性DC，在对博来霉素应答的纤维化阶段浸润治疗动物的肺这些DC是表达CD 40、CD 86和CD 83的成熟DC。它们与表达CD 44、CD 40 L和CD 28的最近激活的记忆T细胞的数量增加相关，表明完全成熟的DC和Ag-经历的T细胞可以在博来霉素肺内驱动有效的效应免疫应答。最重要的是，当DC被VAG 539（一种最近描述的新的免疫调节剂）灭活时，VAG 539治疗减弱了博来霉素肺损伤的标志。这些发现将肺DCs确定为在博来霉素模型中潜在地能够维持肺炎症和纤维化的关键促炎细胞
Rationale Lung dendritic cells (DCs) have been shown to accumulate in human fibrotic lung disease, but little is known concerning a role for DCs in the pathogenesis of fibrotic lung.Objectives: To characterize lung DCs in an in vivo model of bleomycin-induced pulmonary fibrosis in mice.Methods: We characterized the kinetics and activation of pulmonary DCs during the course of bleomycin-induced lung injury by flow cytometry on lung single-cell suspensions. We also characterized the lymphocytes accumulating in bleomycin lung and the chemokines susceptible to favor the recruitment of immune cells.Measurements and Main Results: We show, for the first time, that increased numbers of CD11c(+)/major histocompatibility complex class II+ DCs, including CD11b(hl) monocyte-derived inflammatory DCs, infiltrate the lung of treated animals during the fibrotic phase of the response to bleomycin These DCs are mature DCs expressing CD40, CD86, and CD83. They are associated with increased numbers of recently activated memory T cells expressing CD44, CD40L, and CD28, suggesting that fully mature DCs and Ag-experienced T cells can drive an efficient effector immune response within bleomycin lung Most importantly, when DCs are inactivated with VAG539, a recently described new immunomodulator, VAG539 treatment attenuates the hallmarks of bleomycin lung injury.Conclusions: These findings identify lung DCs as key proinflammatory cells potentially able to sustain pulmonary inflammation and fibrosis in the bleomycin model