Immunometabolism and Molecular Signaling in Systemic Inflammation: Connecting Acute Stress to Chronic Diseases

Systemic inflammation research occupies a pivotal position at the intersection of immunology, metabolism, and disease pathogenesis. Recent advances have revealed that inflammation is not a transient or isolated process but rather a complex continuum linking acute physiological stress to chronic pathology. Acute systemic insults—such as sepsis, severe trauma, or ischemia-reperfusion injury—trigger profound metabolic reprogramming in immune and stromal cells. These shifts include alterations in oxidative phosphorylation, glycolytic flux, and tricarboxylic acid (TCA) cycle dynamics, which extend beyond energy provision to serve as key mediators of gene expression and chromatin remodeling. Studies have shown that metabolites such as succinate, lactate, and itaconate can act as signaling molecules that drive immune cell adaptation, polarization, and long-term tolerance. Despite these insights, key uncertainties remain regarding the molecular checkpoints that dictate whether an acute inflammatory episode resolves or transitions into persistent malfunction, fueling chronic diseases such as fibrosis, cardiovascular injury, and immune exhaustion. Deciphering these mechanistic bridges represents a central challenge in translational immunometabolism.This Research Topic aims to delineate the biochemical and molecular pathways that connect acute systemic inflammation to chronic disease, specifically through the lens of cellular metabolism. The goal is to identify how immune cell fate and intercellular communication are governed by metabolic intermediates, enzymes, and transcriptional regulators. Fundamental questions include: Which metabolite-sensing pathways dictate immune cell memory or tolerance? How do metabolic signatures propagate persistent inflammation across tissue niches? By integrating high-resolution biochemical analyses with systems-level modeling, this topic seeks to uncover molecular targets that can be leveraged to restore immune-metabolic homeostasis. Ultimately, the overarching objective is to redefine therapeutic approaches to inflammation by addressing its metabolic roots rather than its downstream manifestations.The scope of this Research Topic encompasses experimental, mechanistic, and translational studies aimed at elucidating immunometabolic networks in systemic inflammation. The focus is limited to investigations providing direct biochemical or molecular evidence, while purely descriptive or computational works without empirical validation fall beyond its boundaries. To gather further insights into immunometabolic signaling and chronic inflammatory transitions, we welcome articles addressing, but not limited to, the following themes: • Bioenergetic reprogramming in innate and adaptive immune cells during acute inflammatory stress • Mitochondrial dysfunction, dynamics, and redox signaling in sustaining inflammation • Metabolite-mediated epigenetic modifications driving immune memory or tolerance (e.g., lactylation, succinylation) • Crosstalk between immune and parenchymal cells promoting chronic sequelae such as fibrosis or metabolic syndrome • Pharmacological and genetic strategies to correct cellular metabolic derangements • Integration of multi-omics approaches to map the immunometabolic landscape of inflammatory diseases Topic editors: Fengyun Wang, Zhiyong Peng, Chang Hu, Jiahao Zhang Source: https://www.frontiersin.org/research-topics/80578/immunometabolism-and-molecular-signaling-in-systemic-inflammation-connecting-acute-stress-to-chronic-diseases