Immunometabolic reprogramming: a working framework for disease development, endotype differentiation, and therapeutic considerations in pediatric asthma
Year: 2026
Type: review
Abstract: Background: Paediatric asthma exhibits marked clinical heterogeneity and cannot be simply considered the childhood counterpart of adult asthma. Early-life environmental exposures can reshape immune-cell metabolic programs and potentially drive long-lasting inflammatory phenotypes. Existing explanatory frameworks for paediatric asthma largely centre on Th2-related inflammation, epithelial-alarm signalling and neuro-immune crosstalk, while the contributions of immunometabolic processes to disease endotypes remain under-summarised. Objective: This review collates available evidence regarding metabolic reprogramming in the pathogenesis of paediatric asthma and provides an integrated immunometabolic perspective on this condition. Results: Summarized evidence covers immunometabolic changes across key airway-resident and infiltrating cell populations. Discussion addresses core paediatric-specific biological features, including early-life developmental windows, virus-related trained immunity, obese asthma, circadian-sleep interactions, neuro-metabolic-immune communication and metabolomics-based endotyping. The framework is organized around substrate competition rather than a glycolysis-versus-OXPHOS binary, because Tregs, M2-like macrophages and pathogenic ILC2s share lipid and amino-acid pools but exert opposing functions. From these observations emerges a testable "Metabolic Latching Model" of how early-life insults establish persistent inflammatory memory through metabolism-epigenetic coupling, with "latching" operationally defined by exposure removal and persistence beyond responding-cell turnover. Group 2 innate lymphoid cells (ILC2s) and the Treg-to-effector balance are placed at the centre of this framework. Three hypotheses are prioritised as feasible with current technology: H1 (monocyte glycolytic baseline predicting wheeze-to-asthma transition), H4 (metabolic intervention in obese asthma), and H6 (the HDAC2-GSH/butyrate axis in steroid sensitivity). Conclusion: Current evidence suggests that immunometabolic reprogramming serves as one plausible contributing factor for the heterogeneity of paediatric asthma. This conceptual framework may bridge molecular metabolic findings and paediatric clinical contexts, and inform future mechanistic and clinical studies in this research area.
Source: Frontiers in Immunology
Authors: Kaiwen Zheng, Ran Ma, Yingqian Zhang
Institution: Hebei Medical University
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,801
OpenAlex ID: W7222913673