CD103+ dendritic cell-fibroblast crosstalk via TLR9, TDO2, and AHR signaling drives lung fibrogenesis.

ABSTRACT: Idiopathic pulmonary fibrosis (IPF) is characterized by progressive scarring and loss of lung function. With limited treatment options, patients die from the disease within 2-5 years. The molecular pathogenesis underlying the immunologic changes that occur in IPF is poorly understood. We characterize noncanonical aryl-hydrocarbon receptor (ncAHR) signaling in DCs as playing a role in the production of IL-6 and increased IL-17+ cells, promoting fibrosis. TLR9 signaling in myofibroblasts is shown to regulate production of TDO2, which converts tryptophan into the endogenous AHR ligand kynurenine. Mice with augmented ncAHR signaling were created by crossing mice harboring a floxed AHR exon 2 deletion (AHRΔex2) with mice harboring a CD11c-Cre. Bleomycin (blm) was used to study fibrotic pathogen

SUBMITTER: Carter H 

PROVIDER: S-EPMC11949071 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature