Aryl Hydrocarbon Receptor Is Dispensable for the Early Transcriptional Response of Mouse Macrophages to Type I Interferon

Type I interferon (IFN-I) signaling is essential in the homeostasis and activation of immune cells, and macrophages play a central role in the IFN-I system. Dysregulation leads to tissue damage and autoimmunity, and IFN-I signaling needs to be tightly fine-tuned. One reported mechanism involves interactions with the transcription factor aryl hydrocarbon receptor (AhR). However, it remains to be determined whether AhR is required for the early transcriptional response of macrophages to IFN-I. Here we used macrophages from genetically deficient mice to investigate the involvement of AhR in the induction of early IFN-I-driven responses. We show that constitutive AhR deficiency does not impair the canonical transcriptional response to IFN-I in bone marrow-derived macrophages nor the expression of IFN-stimulated molecules by peritoneal macrophages upon in vivo exposure. These findings contrast with observations made in other cell types, in particular astrocytes and lung cancer cells, and support the notion of a context-dependent crosstalk between AhR and IFN-I-dependent signaling.