1 Department of Experimental Medical Science and.
Am J Respir Crit Care Med. 2015 Jun 1;191(11):1232-41. doi: 10.1164/rccm.201410-1861OC.
End-stage chronic obstructive pulmonary disease (COPD) is associated with an accumulation of pulmonary lymphoid follicles. IL-17A is implicated in COPD and pulmonary lymphoid neogenesis in response to microbial stimuli. We hypothesized that IL-17A is increased in peripheral lung tissue during end-stage COPD and also directly contributes to cigarette smoke-induced lymphoid neogenesis.
To characterize the tissue expression and functional role of IL-17A in end-stage COPD.
Automated immune detection of IL-17A and IL-17F was performed in lung tissue specimens collected from patients with Global Initiative for Chronic Obstructive Lung Disease stage I-IV COPD, and smoking and never-smoking control subjects. In parallel, Il17a(-/-) mice and wild-type control animals were exposed to cigarette smoke for 24 weeks, and pulmonary lymphoid neogenesis was assessed.
Tissue expression of IL-17A and IL-17F was increased in COPD and correlated with lung function decline. IL-17A was significantly elevated in severe to very severe COPD (Global Initiative for Chronic Obstructive Lung Disease III/IV) compared with both smokers and never-smokers without COPD. Although CD3(+) T cells expressed IL-17A in very severe COPD, most IL-17A(+) cells were identified as tryptase-positive mast cells. Attenuated lymphoid neogenesis and reduced expression of the B-cell attracting chemokine C-X-C motif ligand (CXCL) 12 was observed in cigarette smoke-exposed Il17a(-/-) mice. CXCL12 was also highly expressed in lymphoid follicles in COPD lungs, and the pulmonary expression was significantly elevated in end-stage COPD.
IL-17A in the peripheral lung of patients with severe to very severe COPD may contribute to disease progression and development of lymphoid follicles via activation of CXCL12.
终末期慢性阻塞性肺疾病（COPD）与肺部淋巴滤泡的积累有关。IL-17A 与 COPD 以及对微生物刺激的肺淋巴新生成有关。我们假设在终末期 COPD 期间，外周肺组织中 IL-17A 增加，并且直接导致香烟烟雾引起的淋巴新生成。
描述 IL-17A 在终末期 COPD 中的组织表达和功能作用。
对来自全球慢性阻塞性肺疾病（GOLD）I-IV 期 COPD 患者和吸烟及不吸烟对照者的肺组织标本进行 IL-17A 和 IL-17F 的自动免疫检测。同时，对 Il17a(-/-) 小鼠和野生型对照动物进行 24 周香烟烟雾暴露，并评估肺部淋巴新生成。
IL-17A 和 IL-17F 的组织表达在 COPD 中增加，并与肺功能下降相关。与吸烟者和不吸烟者无 COPD 相比，IL-17A 在严重至非常严重 COPD（GOLD III/IV）中显著升高。尽管 CD3(+) T 细胞在非常严重的 COPD 中表达了 IL-17A，但大多数 IL-17A(+)细胞被鉴定为糜蛋白酶阳性肥大细胞。在香烟烟雾暴露的 Il17a(-/-) 小鼠中，观察到淋巴新生成减弱和 B 细胞吸引趋化因子 C-X-C 基序配体（CXCL）12 的表达减少。在 COPD 肺中也观察到 CXCL12 在淋巴滤泡中的高表达，并且在终末期 COPD 中肺表达显著升高。
严重至非常严重 COPD 患者外周肺中的 IL-17A 可能通过激活 CXCL12 促进疾病进展和淋巴滤泡的发展。
