合成双调蛋白的致病性记忆Th2细胞诱导嗜酸性粒细胞分泌骨桥蛋白并促进气道纤维化

2018/11/02

   摘要
   记忆T细胞提供持久的免疫保护,并且不同亚群记忆T细胞驱动慢性炎性疾病,例如哮喘。哮喘是一种慢性过敏性炎症性疾病,伴有气道重塑,包括纤维化改变。诱导气道纤维化改变的免疫机制仍然未知。我们发现白细胞介素-33(IL-33)通过IL-33受体ST2hi记忆T辅助细胞2(Th2)细胞,增强了双调蛋白的合成。双调蛋白-表皮生长因子受体(EGFR)介导的信号传导直接将嗜酸性粒细胞重编程为炎症状态,骨桥蛋白(一种关键的促纤维化免疫调节蛋白)表达增高。合成IL-5的记忆Th2细胞和合成双调蛋白的记忆Th2细胞似乎通过共同作用促进了肺纤维化。来自嗜酸性粒细胞性慢性鼻窦炎患者的息肉分析显示,纤维化伴有合成双调蛋白的CRTH2hiCD161hiCD45RO+CD4+ Th2细胞和合成骨桥蛋白的嗜酸性粒细胞的积聚。因此,IL-33-双调蛋白-骨桥蛋白轴诱导嗜酸性粒细胞性气道炎症中的纤维化反应,并且是治疗由慢性过敏性疾病诱导的纤维化的潜在靶标。。

 
(中日友好医院呼吸与危重症医学科 顾宪民 摘译 林江涛 审校)
(Immunity. 2018 Jul 17;49(1):134-150.)


 
 
 
Amphiregulin-Producing Pathogenic Memory T Helper 2 Cells Instruct Eosinophils to Secrete Osteopontin and Facilitate Airway Fibrosis.
 
Morimoto Y, Hirahara K, Kiuchi M, Wada T, Ichikawa T, Kanno T, Okano M, Kokubo K, Onodera A, Sakurai D, Okamoto Y, Nakayama T.
 
Summary
Memory T cells provide long-lasting protective immunity, and distinct subpopulations of memory T cells drive chronic inflammatory diseases such as asthma. Asthma is a chronic allergic inflammatory disease with airway remodeling including fibrotic changes. The immunological mechanisms that induce airway fibrotic changes remain unknown. We found that interleukin-33 (IL-33) enhanced amphiregulin production by the IL-33 receptor, ST2hi memory T helper 2 (Th2) cells. Amphiregulin-epidermal growth factor receptor (EGFR)-mediated signaling directly reprogramed eosinophils to an inflammatory state with enhanced production of osteopontin, a key profibrotic immunomodulatory protein. IL-5-producing memory Th2 cells and amphiregulin-producing memory Th2 cells appeared to cooperate to establish lung fibrosis. The analysis of polyps from patients with eosinophilic chronic rhinosinusitis revealed fibrosis with accumulation of amphiregulin-producing CRTH2hiCD161hiCD45RO+CD4+ Th2 cells and osteopontin-producing eosinophils. Thus, the IL-33-amphiregulin-osteopontin axis directs fibrotic responses in eosinophilic airway inflammation and is a potential target for the treatment of fibrosis induced by chronic allergic disorders.




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