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Iron controls the development of airway hyperreactivity by regulating ILC2 metabolism and effector function

GSE262210 Mus musculus Expression profiling by high throughput sequencing 9 samples Submitted 2024/05/21 Platform GPL19057
Summary
Group 2 innate lymphoid cells (ILC2s) rapidly induce a type 2 inflammation in the lungs in response to allergens. Here, we focused on the role of iron – a critical nutritional trace element – on ILC2 function and asthma pathogenesis. In the lungs, transferrin receptor 1 (TfR1) is rapidly upregulated and functional during ILC2 activation, while blocking transferrin uptake reduces ILC2 expansion and activation. Iron deprivation reprograms ILC2 metabolism, inducing a HIF-1a-driven upregulation of glycolysis and inhibition of oxidative mitochondrial activity. Consequently, in vivo iron chelation or induction of hypoferremia notably reduces the development of airway hyperreactivity in experimental models of ILC2-driven allergic asthma. Human circulating ILC2s rapidly induce TfR1 during activation, while iron deprivation reduces effector functions. Finally, we found a negative relation between circulating ILC2 TfR1 expression and airway function in cohorts of patients with asthma. Collectively, our studies define cellular iron as a critical regulator of ILC2 function.
Published in
Iron controls the development of airway hyperreactivity by regulating ILC2 metabolism and effector function
Hurrell BP, Sakano Y, Shen S et al. · Science translational medicine 2024 · PMID 38718131 · doi:10.1126/scitranslmed.adk4728
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Also filed as BioProject PRJNA1090805 and SRA study SRP497179. Searching any of these in the dataset finder brings you back here.

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