URL: https://www.cell.com/cell-reports/fulltext/S2211-1247(22)01278-5?
Journal: Cell Reports
Publication Date: 09/2022
Summary: Ketone bodies are increasingly understood to have regulatory effects on immune cell function, with β-hydroxybutyrate (BHB) exerting a predominantly anti-inflammatory response. Dietary strategies to increase endogenous ketone body availability such as the ketogenic diet (KD) have recently been shown to alleviate inflammation of the respiratory tract. However, the role of BHB has not been addressed. Here, we observe that BHB suppresses group 2 innate lymphoid cell (ILC2)-mediated airway inflammation. Central to this are mast cells, which support ILC2 proliferation through interleukin-2 (IL-2). Suppression of the mast cell/IL-2 axis by BHB attenuates ILC2 proliferation and the ensuing type 2 cytokine response and immunopathology. Mechanistically, BHB directly inhibits mast cell function in part through GPR109A activation. Similar effects are achieved with either the KD or 1,3-butanediol. Our data reveal the protective role of BHB in ILC2-driven airway inflammation, which underscores the potential therapeutic value of ketone body supplementation for the management of asthma.
Key Takeaways
Ketone bodies produced during a ketogenic diet have an anti-inflammatory effect. These ketones have even been shown to decrease inflammation in the lungs by suppressing an inflammatory cell type called mast cells. Therefore, ketogenic diets can be used as a supplemental treatment for asthma.
