IL-18 associated with lung lymphoid aggregates drives IFNγ production in severe COPD.
IL-18 associated with lung lymphoid aggregates drives IFNγ production in severe COPD.
复制标题
与肺淋巴骨料相关的IL-18在严重COPD中驱动IFNγ产生。
DOI：
10.1186/s12931-017-0641-7
复制
发表时间：
2017-08-22
影响因子：
5.8
通讯作者：
Finch DK
中科院分区：
文献类型：
--
作者：
Briend E;Ferguson GJ;Mori M;Damera G;Stephenson K;Karp NA;Sethi S;Ward CK;Sleeman MA;Erjefält JS;Finch DK
干扰素γ（IFNγ）释放增加发生在慢性阻塞性肺疾病（COPD）肺部。IFNγ支持最佳的病毒清除，但如果失调，可能会增加肺组织的破坏。本研究调查了稳定期和加重期痰液中与IFNγ最密切相关的介质，并试图阐明小鼠淋巴结中IFNγ先天产生的空间要求，以观察这种微环境细胞组织是否与COPD肺中IFNγ的产生相关。我们发现严重疾病中三级卵泡的形成改变了IFNγ产生的主要机制驱动因素，因为产生IFNγ的关键调节因子白细胞介素-18的细胞与这些结构高度相关。COPD痰液中IL-1家族细胞因子与IFNγ的相关性我们观察到COPD肺中IL-18的主要来源是淋巴聚集体中的髓样细胞，并且IL-18在严重疾病中增加。当IL-18产生细胞和应答细胞非常接近时，从感染的上皮或从活化的髓样细胞释放的IL-18在驱动IFNγ中更占优势。与控制淋巴器官中感染扩散的严格调节不同，随着疾病进展，IL-18表达细胞和应答细胞之间的这种局部界面在肺中得到越来越多的支持，从而增加了其通过IFNγ增加组织损伤的可能性。本文的在线版本（doi：10.1186/s12931-017-0641-7）包含补充材料，可供授权用户使用。
Increased interferon gamma (IFNγ) release occurs in Chronic Obstructive Pulmonary Disease (COPD) lungs. IFNγ supports optimal viral clearance, but if dysregulated could increase lung tissue destruction. The present study investigates which mediators most closely correlate with IFNγ in sputum in stable and exacerbating disease, and seeks to shed light on the spatial requirements for innate production of IFNγ, as reported in mouse lymph nodes, to observe whether such microenvironmental cellular organisation is relevant to IFNγ production in COPD lung. We show tertiary follicle formation in severe disease alters the dominant mechanistic drivers of IFNγ production, because cells producing interleukin-18, a key regulator of IFNγ, are highly associated with such structures. Interleukin-1 family cytokines correlated with IFNγ in COPD sputum. We observed that the primary source of IL-18 in COPD lungs was myeloid cells within lymphoid aggregates and IL-18 was increased in severe disease. IL-18 released from infected epithelium or from activated myeloid cells, was more dominant in driving IFNγ when IL-18-producing and responder cells were in close proximity. Unlike tight regulation to control infection spread in lymphoid organs, this local interface between IL-18-expressing and responder cell is increasingly supported in lung as disease progresses, increasing its potential to increase tissue damage via IFNγ. The online version of this article (doi:10.1186/s12931-017-0641-7) contains supplementary material, which is available to authorized users.
登录
查看更多内容
影响因子：
3.7
作者：
Piper SC;Ferguson J;Kay L;Parker LC;Sabroe I;Sleeman MA;Briend E;Finch DK
通讯作者：
Finch DK
影响因子：
8
作者：
通讯作者：
--
影响因子：
168.9
作者：
Brusselle, Guy G.;Joos, Guy F.;Bracke, Ken R.
通讯作者：
Bracke, Ken R.
影响因子：
15.9
作者：
Ma, B;Kang, MJ;Elias, JA
通讯作者：
Elias, JA
影响因子：
24.3
作者：
Imaoka, H.;Hoshino, T.;Aizawa, H.
通讯作者：
Aizawa, H.