美国加州大学Tien Peng研究组发现肺基质失调通过增强常驻淋巴细胞抑制上皮干细胞库导致肺气肿加重。2023年2月22日，国际知名学术期刊《免疫》发表了这一成果。
他们试图在肺气肿中定义这些相互作用，肺气肿是一种以感染性加重和肺泡上皮缺失为特征的进行性疾病。人肺气肿的单细胞分析揭示了组织驻留淋巴细胞（TRL）的扩张。小鼠研究确定了表达Hhip的TRL的基质生态位，Hhip是一种在肺气肿中下调的疾病变异基因。Hhip的基质特异性缺失诱导了由过度活跃的刺猬-IL-7轴介导的肺中TRL的地形扩张。3D免疫干细胞类器官和病毒恶化的动物模型表明，扩增的TRL通过干扰素γ（IFNγ）抑制肺泡干细胞生长。
最后，他们发现了一个IFNγ敏感的人肺泡干细胞亚群，该亚群在肺气肿中优先丢失。因此，他们描绘了肺中的基质 - 淋巴细胞 - 上皮干细胞轴，该轴被疾病变异基因修饰并赋予宿主对肺气肿的易感性。
据悉，异常的组织免疫相互作用是各种慢性肺部疾病的标志。
附：英文原文
Title: Dysregulated lung stroma drives emphysema exacerbation by potentiating resident lymphocytes to suppress an epithelial stem cell reservoir
Author: Chaoqun Wang, Ben Hyams, Nancy C. Allen, Kelly Cautivo, Kiara Monahan, Minqi Zhou, Madelene W. Dahlgren, Carlos O. Lizama, Michael Matthay, Paul Wolters, Ari B. Molofsky, Tien Peng
Issue&Volume: 2023-02-22
Abstract: Aberrant tissue-immune interactions are the hallmark of diverse chronic lung diseases.Here, we sought to define these interactions in emphysema, a progressive disease characterizedby infectious exacerbations and loss of alveolar epithelium. Single-cell analysisof human emphysema lungs revealed the expansion of tissue-resident lymphocytes (TRLs).Murine studies identified a stromal niche for TRLs that expresses Hhip, a disease-variant gene downregulated in emphysema. Stromal-specific deletion ofHhip induced the topographic expansion of TRLs in the lung that was mediated by a hyperactivehedgehog-IL-7 axis. 3D immune-stem cell organoids and animal models of viral exacerbationsdemonstrated that expanded TRLs suppressed alveolar stem cell growth through interferongamma (IFNγ). Finally, we uncovered an IFNγ-sensitive subset of human alveolar stemcells that was preferentially lost in emphysema. Thus, we delineate a stromal-lymphocyte-epithelialstem cell axis in the lung that is modified by a disease-variant gene and confershost susceptibility to emphysema.
DOI: 10.1016/j.immuni.2023.01.032
Source: https://www.cell.com/immunity/fulltext/S1074-7613(23)00044-4
Immunity：《免疫》，创刊于1994年。隶属于细胞出版社，最新IF：43.474
官方网址：https://www.cell.com/immunity/home
投稿链接：https://www.editorialmanager.com/immunity/default.aspx
本期文章：《免疫》：Online/在线发表
