| First Author | Wang C | Year | 2023 |
| Journal | Immunity | Volume | 56 |
| Issue | 3 | Pages | 576-591.e10 |
| PubMed ID | 36822205 | Mgi Jnum | J:334907 |
| Mgi Id | MGI:7448319 | Doi | 10.1016/j.immuni.2023.01.032 |
| Citation | Wang C, et al. (2023) Dysregulated lung stroma drives emphysema exacerbation by potentiating resident lymphocytes to suppress an epithelial stem cell reservoir. Immunity 56(3):576-591.e10 |
| abstractText | Aberrant tissue-immune interactions are the hallmark of diverse chronic lung diseases. Here, we sought to define these interactions in emphysema, a progressive disease characterized by infectious exacerbations and loss of alveolar epithelium. Single-cell analysis of 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 of Hhip induced the topographic expansion of TRLs in the lung that was mediated by a hyperactive hedgehog-IL-7 axis. 3D immune-stem cell organoids and animal models of viral exacerbations demonstrated that expanded TRLs suppressed alveolar stem cell growth through interferon gamma (IFNgamma). Finally, we uncovered an IFNgamma-sensitive subset of human alveolar stem cells that was preferentially lost in emphysema. Thus, we delineate a stromal-lymphocyte-epithelial stem cell axis in the lung that is modified by a disease-variant gene and confers host susceptibility to emphysema. |
