Plasmacytoid dendritic cells in the intestine preferentially produce interferon lambda at homeostasis contributing to tonic localized innate immune responses 2597

Abstract Description Interferon-stimulated genes (ISGs) are expressed in localized regions of the mouse intestinal epithelium dependent on interferon lambda (IFN-λ) and provide preemptive protection from viral infections. Here, we demonstrate that a major source of homeostatic IFN-λ is a population of epithelium-associated plasmacytoid dendritic cells (pDC). The magnitude of localized IFN-stimulated response is reduced upon pDC depletion, and pDC deficient in IFN-λ production are incapable of stimulating a homeostatic ISG response in the epithelium. Additionally, this population of epithelium-associated pDC is recruited to the gut by bacterial microbiota and preferentially expresses IFN-λ but virtually no type I interferons by scRNAseq. This study implicates pDC as important mediators of tonic IFN-λ signaling in the gut, with notably minimal type I IFN contributions, expanding their role as critical IFN producing cells. Funding Sources Funding for this work was provided by National Institutes of Health grants AI130055 (TJN) and T32-AI007472 (JVW) and OHSU. Topic Categories Mucosal and Regional Immunology (MUC)