Interleukin-11 causes alveolar type 2 cell dysfunction and prevents alveolar regeneration

Benjamin Ng (), Kevin Y. Huang, Chee Jian Pua, Sivakumar Viswanathan, Wei-Wen Lim, Fathima F. Kuthubudeen, Yu-Ning Liu, An An Hii, Benjamin L. George, Anissa A. Widjaja, Enrico Petretto and Stuart A. Cook ()
Additional contact information
Benjamin Ng: National Heart Center Singapore
Kevin Y. Huang: Duke-National University of Singapore Medical School
Chee Jian Pua: National Heart Center Singapore
Sivakumar Viswanathan: Duke-National University of Singapore Medical School
Wei-Wen Lim: National Heart Center Singapore
Fathima F. Kuthubudeen: Duke-National University of Singapore Medical School
Yu-Ning Liu: Duke-National University of Singapore Medical School
An An Hii: National Heart Center Singapore
Benjamin L. George: Duke-National University of Singapore Medical School
Anissa A. Widjaja: Duke-National University of Singapore Medical School
Enrico Petretto: Duke-National University of Singapore Medical School
Stuart A. Cook: National Heart Center Singapore

Nature Communications, 2024, vol. 15, issue 1, 1-16

Abstract: Abstract 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.

Date: 2024
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-024-52810-8 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-52810-8

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-024-52810-8

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().