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

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 c

SUBMITTER: Ng B 

PROVIDER: S-EPMC11448503 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature