The substrate is not enough: receptor-restricted metabolic targeting of ILC2s in allergic airway disease.
- 1Department of Immunology and Immune Therapeutics, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Abstract
Opposing metabolic perturbations of group 2 innate lymphoid cells (ILC2s) - such as upregulating or downregulating glycolysis and suppressing or preserving oxidative phosphorylation - repeatedly produce the same reduction in airway hyperreactivity. We argue that this does not reflect a contradiction in the literature, but rather a defining property of these cells: ILC2s are tissue-resident sentinels whose metabolism is calibrated by cell-surface receptor expression, local nutrient availability, microenvironmental conditions (such as oxygen tension and pH), and metabolic competition with neighboring immune cells, particularly the regulatory T (Treg) cells that restrain them. Since ILC2 pathogenicity requires the coordinated operation of both the glycolytic and oxidative arms, therapeutic interventions are effective in proportion to how much they restrict their metabolic plasticity rather than which specific pathway they target. Given that ILC2s co-localize with, and are likely to share their nutrient supply with, Treg cells and other neighboring populations, this distinction has major clinical implications; it separates targeted therapies that selectively disarm the effector from nonselective strategies that starve the effector and its suppressor together.
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BibTeX
@article{wang2026substrate,
title = {{The substrate is not enough: receptor-restricted metabolic targeting of ILC2s in allergic airway disease.}},
author = {Bowen Wang and Vanessa-Vivien Pesold and Omid Akbari},
journal = {Immunometabolism (Cobham, Surrey)},
year = {2026},
month = oct,
doi = {10.1097/in9.0000000000000094},
url = {https://europepmc.org/article/MED/42997609},
note = {CC BY},
}
RIS
TY - JOUR
TI - The substrate is not enough: receptor-restricted metabolic targeting of ILC2s in allergic airway disease.
AU - Bowen Wang
AU - Vanessa-Vivien Pesold
AU - Omid Akbari
PY - 2026
DA - 2026/10/01
JO - Immunometabolism (Cobham, Surrey)
DO - 10.1097/in9.0000000000000094
UR - https://europepmc.org/article/MED/42997609
AB - Opposing metabolic perturbations of group 2 innate lymphoid cells (ILC2s) - such as upregulating or downregulating glycolysis and suppressing or preserving oxidative phosphorylation - repeatedly produce the same reduction in airway hyperreactivity. We argue that this does not reflect a contradiction in the literature, but rather a defining property of these cells: ILC2s are tissue-resident sentinels whose metabolism is calibrated by cell-surface receptor expression, local nutrient availability, microenvironmental conditions (such as oxygen tension and pH), and metabolic competition with neighboring immune cells, particularly the regulatory T (Treg) cells that restrain them. Since ILC2 pathogenicity requires the coordinated operation of both the glycolytic and oxidative arms, therapeutic interventions are effective in proportion to how much they restrict their metabolic plasticity rather than which specific pathway they target. Given that ILC2s co-localize with, and are likely to share their nutrient supply with, Treg cells and other neighboring populations, this distinction has major clinical implications; it separates targeted therapies that selectively disarm the effector from nonselective strategies that starve the effector and its suppressor together.
SN - 2633-0407
ER -