| Title: |
Interleukin-11 causes alveolar type 2 cell dysfunction and prevents alveolar regeneration |
| Authors: |
Ng, B; Huang, KY; Pua, CJ; Viswanathan, S; Lim, W-W; Kuthubudeen, FF; Liu, Y-N; Hii, AA; George, BL; Widjaja, AA; Petretto, E; Cook, SA |
| Publisher Information: |
Nature Portfolio |
| Publication Year: |
2024 |
| Collection: |
Imperial College London: Spiral |
| Description: |
In lung disease, persistence of KRT8-expressing aberrant basaloid cells in the alveolar epithelium is associated with impaired tissue regeneration and pathological tissue remodeling. We analyzed single cell RNA sequencing datasets of human interstitial lung disease and found the profibrotic Interleukin-11 (IL11) cytokine to be highly and specifically expressed in aberrant KRT8+ basaloid cells. IL11 is similarly expressed by KRT8+ alveolar epithelial cells lining fibrotic lesions in a mouse model of interstitial lung disease. Stimulation of alveolar epithelial cells with IL11 causes epithelial-to-mesenchymal transition and promotes a KRT8-high state, which stalls the beneficial differentiation of alveolar type 2 (AT2)-to-AT1 cells. Inhibition of IL11-signaling in AT2 cells in vivo prevents the accumulation of KRT8+ cells, enhances AT1 cell differentiation and blocks fibrogenesis, which is replicated by anti-IL11 therapy. These data show that IL11 inhibits reparative AT2-to-AT1 differentiation in the damaged lung to limit endogenous alveolar regeneration, resulting in fibrotic lung disease. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
Nature Communications; http://hdl.handle.net/10044/1/115703 |
| DOI: |
10.1038/s41467-024-52810-8 |
| Availability: |
http://hdl.handle.net/10044/1/115703; https://doi.org/10.1038/s41467-024-52810-8 |
| Rights: |
© The Author(s) 2024 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. ; https://creativecommons.org/licenses/by/4.0/ |
| Accession Number: |
edsbas.1000D676 |
| Database: |
BASE |