Metabolic-Epigenetic-Immune Regulatory Networks Emerge as Therapeutic Targets in Inflammation and Disease
核心洞察
Metabolic reprogramming is now recognized as a hallmark of chronic inflammatory disorders, metabolic diseases, and cancer (搜索), with metabolic intermediates acting as signaling molecules and substrates for epigenetic modifications.
Epigenetic mechanisms, including histone modifications, DNA methylation, chromatin remodeling, and non-coding RNAs, coordinate transcriptional programs that regulate immune cell activation and inflammatory responses.
The crosstalk among metabolism, epigenetics, and immune signaling forms integrated regulatory networks whose disruption drives persistent inflammation, immune dysfunction, and pathological tissue remodeling.
Metabolic reprogramming has emerged as a hallmark of numerous pathological conditions, including chronic inflammatory disorders, metabolic diseases, and cancer (搜索). Beyond sustaining energy production, metabolic intermediates function as signaling molecules and substrates for epigenetic modifications, thereby reshaping gene expression and cellular phenotypes. At the same time, epigenetic mechanisms—including histone modifications, DNA methylation, chromatin remodeling, and non-coding RNAs—coordinate transcriptional programs that regulate immune cell activation, inflammatory responses, and tissue homeostasis.
Increasing evidence indicates that metabolism, epigenetics, and immune signaling are tightly interconnected rather than acting independently. Their dynamic crosstalk forms regulatory networks that determine cellular adaptation to stress and disease. Disruption of these networks contributes to persistent inflammation, immune dysfunction, and pathological tissue remodeling, highlighting their importance as emerging therapeutic targets.
An Integrated Regulatory Circuit
Although significant progress has been made in identifying individual metabolic or epigenetic regulators, the integrated regulatory circuits linking cellular metabolism, chromatin dynamics, immune signaling, and disease pathology remain incompletely understood. Recent advances in multi-omics technologies, spatial transcriptomics, epigenomic profiling, and functional genomics have provided unprecedented opportunities to dissect these complex interactions at cellular resolution.
Researchers particularly emphasize studies investigating how metabolic alterations influence epigenetic landscapes, how epigenetic modifications regulate immune cell function and inflammatory signaling, and how feedback loops among these processes contribute to chronic inflammation, metabolic dysfunction, fibrosis, cancer (搜索), and other human diseases. By integrating mechanistic studies with translational research, this line of inquiry seeks to identify novel biomarkers and therapeutic strategies targeting metabolic-epigenetic-immune regulatory axes.
The Immunometabolic Interface
The immune system and metabolic pathways are deeply interconnected, forming a complex regulatory network that influences health and disease. Over the past decade, the emerging field of immunometabolism has revealed how metabolic alterations can shape immune cell development, activation, effector functions, and resolution of inflammation. Conversely, immune responses profoundly influence systemic and cellular metabolism, creating bidirectional interactions that determine disease susceptibility and outcomes.
Beyond systemic effects, tissue- and cell-specific metabolic programs—well described in the context of cancer (搜索)—can locally shape immune cell activation and differentiation, for example through altered metabolite secretion by tumor cells that reprograms the surrounding immune microenvironment. Metabolic disorders such as type 1 diabetes (搜索), obesity (搜索), and metabolic syndrome (搜索) are characterized by chronic low-grade inflammation and immune dysfunction. These alterations have been implicated not only in cardiovascular and metabolic diseases but also in the development and progression of autoimmune conditions and infectious diseases.
Clinical and Translational Implications
Increasing evidence suggests that metabolic reprogramming of immune cells influences tolerance, autoimmunity, host defense, tissue damage, and recovery processes. The intersection between immunometabolism, inflammation, and disease has become particularly relevant in the context of infections: metabolic status can affect susceptibility to pathogens, disease severity, immune-mediated pathology, and therapeutic responses. Likewise, infectious agents can induce profound metabolic changes that contribute to chronic inflammation, immune dysregulation, and long-term complications.
Similar mechanisms are increasingly recognized in autoimmune disorders, where alterations in cellular metabolism regulate the balance between pro-inflammatory and regulatory immune responses. Despite significant advances, many questions remain unanswered regarding the molecular mechanisms linking metabolism to immune function across diverse pathological conditions. A deeper understanding of these processes may reveal novel biomarkers and therapeutic targets capable of modulating immune responses while restoring metabolic homeostasis.
Emerging Therapeutic Strategies
The research agenda spans a broad range of therapeutic modalities. Topics of interest include small molecules, natural products—including traditional Chinese medicine-derived compounds—and therapeutic strategies targeting metabolic-epigenetic-immune regulatory pathways. Additional areas of focus include post-translational modifications and organelle stress in disease pathogenesis, macrophage polarization and inflammatory signaling pathways, and biomarker discovery and translational studies.
Further priorities include immunometabolic regulation of innate and adaptive immune responses, mitochondrial dysfunction, oxidative stress, and inflammatory signaling, as well as trained immunity and metabolic memory. Studies employing cell models, animal models, patient-derived samples, and integrated computational approaches are all encouraged, reflecting the field's commitment to bridging basic mechanistic discovery with clinical translation.