The hidden role of iron: unlocking new therapies for asthma and beyond 9432

Abstract Description Iron is a critical nutritional trace element. With many of the mechanisms involved in systemic iron homeostasis characterized however, attention is now increasingly turning to the role of iron in tissues and immune cells. Notably, we recently reported the critical role of iron on group 2 innate lymphoid cell (ILC2) bioenergetics and development of type 2 airway inflammation. Using several approaches, we showed that iron deprivation reprograms ILC2 metabolism, as the restriction of cellular iron availability reduces the development of airway hyperreactivity in experimental models of ILC2-driven allergic asthma in vivo. Targeting iron systemically in humans may however pose challenges as iron plays diverse and crucial roles in numerous physiological processes affecting human health. Instead of targeting iron, our new transcriptome and metabolome analysis offer insights into iron-regulated mechanisms, particularly those taking place within the mitochondria, that could be targeted independently of iron. We notably found that the effects of iron can be modulated by affecting amino acid biosynthesis that is crucial for proliferation of mammalian cells. Furthermore, we combined pharmacological and genetic approaches to demonstrate that mitochondrial iron import plays a pivotal role in ILC2 function and development of lung inflammation. Taken together, our new studies therefore provide a basis to develop therapies for asthma or other ILC2-driven diseases. Funding Sources National Institutes of Health grant : R01 HL144790, R01 HL151493, R01 AI145813, R01AI169687, R01 HL151769, and R01 HL 159804 (OA) Topic Categories Immediate Hypersensitivity, Asthma, and Allergic Responses (HYP)