IL-33 induces production of autoantibody against autologous respiratory epithelial cells: a potential mechanism for the pathogenesis of COPD
IL-33 induces production of autoantibody against autologous respiratory epithelial cells: a potential mechanism for the pathogenesis of COPD
复制标题
IL-33诱导针对自体呼吸道上皮细胞产生自身抗体：COPD发病机制的潜在机制
DOI：
10.1111/imm.13054
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发表时间：
2019-06-01
期刊：
影响因子：
6.4
通讯作者：
Ying, Sun
中科院分区：
文献类型：
--
作者：
Li, Qin;Hu, Yue;Ying, Sun
人类慢性阻塞性肺疾病（COPD）特征的慢性进行性气道炎症、重塑和肺泡结构损伤的机制尚不清楚。在目前的研究中，我们提出了这样的假设，即这些变化至少部分是由呼吸道上皮警报素（IL-33）诱导的针对气道上皮细胞的自身抗体的产生介导的。用同源的、同源的肺组织溶液和IL-33直接给药到呼吸道或全身产生IgG自身抗体，主要结合自己的肺泡II型上皮细胞，随着Tfh细胞和B2 b细胞在局部纵隔淋巴结的百分比增加。与它对呼吸道上皮细胞的特异性一致，这种自身免疫性炎症主要局限于肺，而不是肝和肾等其他器官。此外，小鼠产生的血清自身抗体不仅与小鼠结合，而且与人肺泡II型上皮细胞结合，表明对常见的跨物种决定因子具有特异性。最后，与对照组相比，COPD患者血清中针对人和鼠肺泡上皮细胞的抗体浓度均显著升高。这些数据与IL-33通过诱导针对肺组织，特别是肺泡II型上皮细胞的自身抗体，导致慢性进行性气道阻塞、炎症和肺泡破坏的假说是一致的。
The mechanisms underlying the chronic, progressive airways inflammation, remodelling and alveolar structural damage characteristic of human chronic obstructive pulmonary disease (COPD) remain unclear. In the present study, we address the hypothesis that these changes are at least in part mediated by respiratory epithelial alarmin (IL-33)-induced production of autoantibodies against airways epithelial cells. Mice immunized with homologous, syngeneic lung tissue lysate along with IL-33 administered directly to the respiratory tract or systemically produced IgG autoantibodies binding predominantly to their own alveolar type II epithelial cells, along with increased percentages of Tfh cells and B2 B-cells in their local, mediastinal lymph nodes. Consistent with its specificity for respiratory epithelial cells, this autoimmune inflammation was confined principally to the lung and not other organs such as the liver and kidney. Furthermore, the serum autoantibodies produced by the mice bound not only to murine, but also to human alveolar type II epithelial cells, suggesting specificity for common, cross-species determinants. Finally, concentrations of antibodies against both human and murine alveolar epithelial cells were significantly elevated in the serum of patients with COPD compared with those of control subjects. These data are consistent with the hypothesis that IL-33 contributes to the chronic, progressive airways obstruction, inflammation and alveolar destruction characteristic of phenotypes of COPD/emphysema through induction ofautoantibodies against lung tissue, and particularly alveolar type II epithelial cells.