Stem cell transplantation uncovers TDO-AHR regulation of lung dendritic cells in herpesvirus-induced pathology.

ABSTRACT: The aryl-hydrocarbon receptor (AHR) is an intracellular sensor of aromatic hydrocarbons that sits at the top of various immunomodulatory pathways. Here, we present evidence that AHR plays a role in controlling IL-17 responses and the development of pulmonary fibrosis in response to respiratory pathogens following bone marrow transplant (BMT). Mice infected intranasally with gamma-herpesvirus 68 (γHV-68) following BMT displayed elevated levels of the AHR ligand, kynurenine (kyn), in comparison with control mice. Inhibition or genetic ablation of AHR signaling resulted in a significant decrease in IL-17 expression as well as a reduction in lung pathology. Lung CD103+ DCs expressed AHR following BMT, and treatment of induced CD103+ DCs with kyn resulted in altered cytokine production in respo

SUBMITTER: Gurczynski SJ 

PROVIDER: S-EPMC7934859 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature