Aryl Hydrocarbon Receptor Activation Ameliorates Acute Respiratory Distress Syndrome through Regulation of Th17 and Th22 Cells in the Lungs
Bryan L. Holloman, Alkeiver S Cannon, Kiesha Wilson, Prakash Nagarkatti, Mitzi Nagarkatti
Abstract
Acute respiratory distress syndrome (ARDS) is a type of respiratory failure that is triggered by a variety of bacterial and viral infections, including the coronavirus SARS-CoV2. ARDS is associated with a hyperimmune response in the lungs that which is challenging to treat. Because of this difficulty, approximately 40% of patients with ARDS die. Thus, it is critical to understand the nature of the immune response that is functional in the lungs during ARDS as well as approaches by which to attenuate it. AhR is a transcription factor that is activated by a variety of endogenous and exogenous environmental chemicals as well as bacterial metabolites. While AhR has been shown to regulate inflammation, its role in ARDS is unclear. In the current study, we provide evidence that AhR activation can attenuate LPS-mediated ARDS through the activation of Th22 cells in the lungs, which are regulated through miR-29b-2-5p. Thus, AhR can be targeted to attenuate ARDS.