image: Tissue injury triggers a dynamic repair niche that is coordinated by metabolic stress, inflammatory and danger signals, and structural or stromal cues. Within this niche, immune cells undergo metabolic adaptation to accommodate local environmental changes and stage-specific repair demands. These adaptive metabolic programs instruct immune effector and repair-associated functions, including host defense, debris clearance, efferocytosis, inflammation resolution, mediator production, angiogenesis, and support for tissue progenitors. Conversely, immune cells can also reshape the local repair niche through metabolite release and their interactions with stromal and epithelial compartments. Balanced immunometabolic regulation promotes regenerative repair and functional recovery, whereas persistent, excessive, or temporally mismatched metabolic activation may drive maladaptive outcomes, such as chronic inflammation, defective clearance, pathological fibrosis or scarring, and long-term tissue dysfunction. Abbreviations: ROS, reactive oxygen species; DAMPs, damage-associated molecular patterns; PAMPs, pathogen-associated molecular patterns; ECM, extracellular matrix; OXPHOS, oxidative phosphorylation; FAO, fatty acid oxidation; AA metabolism, amino acid metabolism; NETs, neutrophil extracellular traps. This figure was created using BioRender (https:// biore nder. com/)
Credit: Professor Di Wang from Zhejiang University, China; Dr. Zheyu Chi from Zhejiang University, China Image source link: https://link.springer.com/article/10.1007/s44466-026-00052-2
A research team led by Professor Di Wang and Dr. Zheyu Chi at Zhejiang University School of Medicine, China, published a comprehensive review on August 17, 2026, in Volume 2, article number 34 of the journal Immunity & Inflammation. The article, titled "Niche-dependent immunometabolic regulation of tissue repair and regeneration," systematically summarizes immunometabolic regulatory mechanisms across six tissue types following injury and compares the differential effects of shared metabolic signals across organs. The authors propose a conceptual framework in which immunometabolism should be understood as an adaptive process shaped by the local repair niche.
Tissue injury triggers a cascade of events including cell death, hypoxia, oxidative stress, nutrient flux changes, inflammatory signals, and extracellular matrix remodeling, collectively forming a dynamic repair microenvironment. Immune cells must continuously adjust their glycolytic, mitochondrial, lipid, amino acid, and redox metabolism to meet the functional demands of each repair stage—clearing pathogens and damaged tissue, resolving inflammation, promoting vascular remodeling, and supporting tissue-resident stem and progenitor cells.
Conversely, immune cells actively reshape the local microenvironment through release of metabolites and repair mediators. Whether this bidirectional metabolic dialogue between immune cells and the tissue microenvironment is appropriately matched to the current repair phase ultimately determines the outcome of tissue repair—functional regeneration or pathological remodeling.
“Different organs face distinct repair demands,” the authors propose. The intestine and skin require rapid restoration of barrier function; the liver relies primarily on mature hepatocyte proliferation for regeneration; the lung must re-establish airway and alveolar structures; skeletal muscle depends on muscle stem cell activation; while the adult heart has very limited regenerative capacity. Consequently, each organ develops its own characteristic metabolic microenvironment with unique functional demands on infiltrating immune cells.
This organ specificity means that the same metabolic pathway or metabolite does not possess fixed "pro-inflammatory" or "pro-repair" properties. Using examples including lactate, succinate, lipid metabolism, itaconate, and redox signaling, the article demonstrates that the same metabolic signal can yield different or even opposing outcomes depending on tissue type, cell population, and repair stage. Thus, rather than simplistically labeling a metabolite as "beneficial" or "harmful," “it is more meaningful to ask: in which tissue, acting on which cells, at what repair stage, and whether it matches the specific repair needs of that organ at that moment,” the authors highlight.
Beyond metabolism, the authors further discuss how tissue mechanics, neural regulation, trained immunity, and inter-organ communication expand the concept of the repair niche. Future immunometabolic interventions should avoid indiscriminate systemic activation or inhibition of a single pathway; instead, they must prioritize organ specificity, cell type specificity, and therapeutic time windows.
In summary, this review argues that immunometabolism in tissue repair is fundamentally a niche-dependent adaptive process. The tissue microenvironment shapes the metabolic state of immune cells, while immune cells, through metabolic reprogramming and intercellular communication, reciprocally determine tissue repair trajectories. This perspective moves immunometabolism research beyond studying "how a specific pathway regulates immune cells" to address the broader question of "how different tissues leverage immunometabolism to meet their specific repair demands." This framework offers new insights into understanding the transitions between regeneration, chronic inflammation, and fibrosis, and provides guidance for developing more precise tissue repair intervention strategies.
Reference
Title of original paper: Niche‑dependent immunometabolic regulation of tissue repair and regeneration
Journal: Immunity & Inflammation
DOI: https://doi.org/10.1007/s44466-026-00052-2
About Immunity & Inflammation
Immunity & Inflammation is a newly launched open-access journal co-published by the Chinese Society for Immunology and Springer Nature under the leadership of Editors-in-Chief Prof. Xuetao Cao and Prof. Jules A. Hoffmann. Immunity & Inflammation aims to publish major scientific questions and cutting-edge advances that explore groundbreaking discoveries and insights across the spectrum of immunity and inflammation, from basic science to translational and clinical research.
Website: https://link.springer.com/journal/44466
About Professor Di Wang from Zhejiang University, China
Dr. Di Wang is a Qiushi Distinguished Professor at Zhejiang University and Director of the Center for Infection and Immunity. He has received numerous honors including the Young Changjiang Scholar Award from the Ministry of Education, the Zhejiang Provincial Natural Science Award (First Class), and the Tan Jiazhen Life Science Innovation Award. His long-term research focuses on immunometabolism, with a series of discoveries identifying key mechanisms and molecular targets in the field.
About Dr. Zheyu Chi from Zhejiang University, China
Dr. Zheyu Chi is a "Platform" Hundred Talents Program Researcher at Zhejiang University. He has received the Zhejiang Provincial Natural Science Award (First Class) and has been selected for the Zhejiang Provincial High-Level Talent Special Support Program. His research focuses on the mechanisms by which immunometabolism regulates inflammation, tissue repair, and aging processes.
Funding information
This work was supported by the National Natural Science Foundation of China (82588302, 82530064, and 82025017 to D.W.; 82522041 and 32370919 to Z.C.), the National Key Research and Development Program of China (2024YFA1803101 and 2024YFA1306802), the Fundamental and Interdisciplinary Disciplines Breakthrough Plan of the Ministry of Education of China (JYB2025XDXM604), the Key Research and Development Program of Zhejiang Province (2025C02163), and the Fundamental Research Funds for the Central Universities (226–2024-00161).
Journal
Immunity & Inflammation
Method of Research
Systematic review
Subject of Research
Not applicable
Article Title
Niche‑dependent immunometabolic regulation of tissue repair and regeneration
Article Publication Date
17-Aug-2026
COI Statement
The authors declare no competing interests.