INTRODUCTION:Parasitic infections remain a major global health challenge involving complex interactions between pathogens and host immunity. Emerging evidence indicates that epigenetic mechanisms, including DNA methylation, histone modifications, chromatin remodeling, and non-coding RNAs, critically regulate immune responses and influence host susceptibility, resistance, and disease progression. METHODS:This review synthesizes current evidence on epigenetic regulation of host immunity during parasitic infections, focusing on mechanisms underlying immune activation, immune evasion, host susceptibility, and parasite persistence. Emerging epigenetic biomarkers and therapeutic strategies targeting epigenetic pathways are also considered. RESULTS:Parasites can manipulate host epigenetic machinery to evade immune surveillance, suppress protective responses, and establish persistent infections. Conversely, epigenetic regulation in immune cells modulates cytokine production, macrophage polarization, T-cell differentiation, and immune memory, thereby influencing infection outcomes. Parasite-derived epigenetic factors and non-coding RNAs may additionally contribute to immune modulation and immunopathology. Epigenetic signatures associated with disease severity and treatment response show potential as biomarkers, while targeting epigenetic pathways may enhance antiparasitic immunity. DISCUSSION:Epigenetic regulation represents a central mechanism governing host-parasite interactions. Integrating advanced approaches, including single-cell epigenomics and spatial transcriptomics, may clarify cell-specific mechanisms and identify novel biomarkers and therapeutic targets. These advances could support personalized strategies to improve antiparasitic treatment and disease outcomes.
BACKGROUND:Neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis are increasingly recognized as disorders influenced not only by intrinsic neural pathology but also by systemic physiological networks, including the gut-brain axis. Emerging evidence highlights physical activity as a potent modulator of this bidirectional communication system, with muscle-derived signals particularly myokines, metabolites, and extracellular vesicles playing a central role. METHODS:This narrative review synthesizes current knowledge on how exercise-induced molecular mediators influence gut microbiota composition, intestinal barrier integrity, immune signaling, and neuroinflammatory pathways. Findings were integrated across the disciplines of neuroscience, microbiology, and exercise physiology to evaluate mechanistic links between muscle-secreted factors and gut-mediated responses. RESULTS:Mechanistic links exist between muscle-secreted factors such as irisin, cathepsin B, BDNF-inducing pathways, and lactate with microbial metabolites including short-chain fatty acids. These interacting pathways demonstrate a combined impact on neuroprotection, synaptic plasticity, and the modulation of disease progression in neurodegenerative conditions. CONCLUSION:Physical activity represents a promising non-pharmacological strategy for modulating the gut-brain axis in neurodegenerative conditions. Understanding the interplay between muscle-derived signals and gut-mediated pathways may open new avenues for targeted interventions aimed at slowing or preventing neurodegenerative decline.
BACKGROUND:Chronic inflammatory disorders represent a major global health burden characterized by persistent immune activation, oxidative stress, and progressive tissue dysfunction. Dysregulated redox signaling has positioned the Kelch-like ECH-associated protein 1 (KEAP1)-nuclear factor erythroid 2-related factor 2 (Nrf2) axis as an emerging therapeutic target. METHODS:This review critically examines the mechanistic architecture and context-dependent regulation of KEAP1-Nrf2 signaling across chronic inflammatory disorders, integrating disease-specific evidence, signaling crosstalk, quantitative preclinical findings, therapeutic modulators, nanoenabled delivery systems, clinical evidence, patent trends, and artificial intelligence-assisted drug discovery strategies. RESULTS:KEAP1-Nrf2 signaling extends beyond antioxidant defense to regulate immunometabolic homeostasis, mitochondrial function, inflammatory signaling, and cellular stress adaptation. Crosstalk with NF-κB, MAPK, PI3K/Akt, and inflammasome-associated pathways contributes to disease-specific inflammatory responses. Preclinical evidence supports natural and synthetic Nrf2 modulators, while nanotechnology-based approaches may improve delivery and tissue specificity. However, dose optimization, bioavailability, off-target effects, long-term safety, and patient heterogeneity remain important translational challenges. CONCLUSION:KEAP1-Nrf2 represents a context-dependent therapeutic axis with substantial potential across chronic inflammatory diseases. Integrating quantitative evidence, precision delivery, biomarker-guided approaches, and computational strategies may facilitate clinical translation while addressing risks associated with sustained pathway activation.
BACKGROUND:Gastric cancer (GC) involves complex immune-metabolic crosstalk, but MR-prioritized immunophenotypes and mediating metabolites remain unclear. METHODS:Two-sample Mendelian randomization (MR) was performed using GWAS summary data for 731 immunophenotypes, 1,400 circulating metabolites, and GC (218,792 European participants). Instruments were selected at p < 1 × 10-5, LD-clumped (r2 < 0.001, 10,000 kb), and filtered for strength (F > 10). IVW served as the primary estimator, with sensitivity and reverse MR analyses. Two-step MR explored metabolite-mediated pathways. Single-cell RNA-seq from 56 samples across three sources was integrated to resolve HLA-DR+ CD4+ T-cell transcriptional states, evaluate GC genetic-risk enrichment via scDRS, and infer cell-cell communication using CellChat. RESULTS:Twenty-six immunophenotypes showed candidate associations with GC. HLA-DR expression on HLA-DR+ CD4+ T cells was inversely associated with GC risk (OR = 0.761, 95% CI 0.634-0.912, FDR q = 0.0393). Reverse MR was not FDR-significant, and MR-Egger indicated no directional pleiotropy. Candidate mediation involved bilirubin degradation product C17H18N2O4(2). Single-cell analysis identified five HLA-DR+ CD4+ T-cell subsets; T1 and T5 showed relatively higher GC genetic-susceptibility enrichment, with T5 exhibiting low CytoTRACE scores. These subsets were linked to immune activation and chemokine signaling. The exploratory TIGIT-NECTIN2 signal was not robustly retained after CellChat sensitivity filtering. CONCLUSION:This study suggests a potential inverse association between HLA-DR+ CD4+ T-cell immunophenotypes and GC risk, with bilirubin-related metabolites as a candidate mediating pathway. Subsets T1/T5 provide candidate directions for future GC immune-prevention research.
Background: γδ T cells are emerging as a promising immunotherapy platform because they combine rapid innate-like effector activity with adaptive immune features and recognize stress-associated signals in a largely MHC-independent manner. Their clinical utility, however, is constrained by pronounced heterogeneity in subset composition, tissue localization, and functional state.Objective: This review aims to summarize the biological principles governing γδ T-cell development, classification, and antigen recognition and to examine how their context-dependent functions inform therapeutic design.Methods: We integrated current evidence on γδ T-cell biology across cancer, infection, and autoimmunity and evaluated the major translational strategies currently being developed.Results: Current strategies include in vivo activation, adoptive transfer, combination regimens, engineered γδ T-cell products, and cell-free approaches such as γδ T-cell-derived extracellular vesicles. However, clinical translation remains limited by product heterogeneity, insufficient expansion and persistence, and incomplete mechanistic resolution.Conclusion: Future development should prioritize mechanism-guided engineering, biomarker-informed development, and better-designed clinical studies.
BACKGROUND:In idiopathic pulmonary fibrosis (IPF), inflammatory signaling and fibrotic remodeling often coexist, yet the mechanism linking these processes remains unclear. Numb, a cell fate determinant protein, has been implicated in tissue remodeling but its role in inflammation - fibrosis coupling is not well defined. METHODS:Public transcriptomic datasets were analyzed to assess NUMB expression patterns and associated pathways. A bleomycin (BLM)-induced mouse model was used for in vivo validation. In vitro, MRC-5 fibroblasts were stimulated with IL-1β and TGF-β1, alone or in combination, followed by Numb siRNA intervention. Cell viability, migration, cytokine secretion, and fibrosis-related protein expression were evaluated. RESULTS:Transcriptomic analysis showed a non-significant but consistent upward trend of NUMB in IPF tissues (p = .18), with pathway-level enrichment in inflammatory and extracellular matrix processes. In BLM-treated mice, IL-1β and TGF-β1 levels were significantly increased (both p < .001), accompanied by upregulation of Numb (p < .05), α-SMA, and Collagen I (both p < .001). In vitro, IL-1β and TGF-β1 synergistically enhanced cell viability and migration (both p < .001), as well as protein expression (p < .001). Numb silencing reduced cytokine secretion (p < .001), cell activation (p < .05-0.001), and fibrosis-related protein expression (p < .001). CONCLUSION:Numb participates in coordinating inflammatory and fibrotic responses in IPF and may act as a regulatory mediator in inflammation - fibrosis coupling.
Background: Antibody-drug conjugates (ADCs) have transformed the treatment of solid tumors by combining the tumor specificity of monoclonal antibodies with highly potent cytotoxic payloads. Advances in ADC engineering have expanded their clinical applications while addressing limitations of conventional chemotherapy and targeted therapies.Methods: We conducted a comprehensive narrative review of the molecular mechanisms, structural design, resistance pathways, clinical translation, and emerging engineering strategies of ADCs in solid tumors, integrating evidence from preclinical and clinical studies.Results: ADC efficacy is governed by antigen selection, linker chemistry, payload characteristics, and drug-to-antibody ratio, which collectively influence pharmacokinetics, tumor penetration, intracellular trafficking, and payload release. Key mechanisms include receptor-mediated internalization, lysosomal processing, bystander killing, immune modulation, and interactions with the tumor microenvironment. Major resistance mechanisms comprise antigen heterogeneity, impaired intracellular trafficking, drug efflux, adaptive DNA repair, and stromal barriers. Emerging innovations-including site-specific conjugation, bispecific and conditionally activated ADCs, novel payloads, biomarker-guided patient selection, and rational combination therapies-are enhancing therapeutic efficacy and expanding targetable tumors.Conclusion: Continued advances in molecular engineering and precision biomarker strategies are redefining ADCs as versatile platforms for precision oncology and may enable broader, potentially tumor-agnostic, applications in solid tumors.
BACKGROUND:The PD-1/PD-L1 axis is a key immune checkpoint that maintains peripheral tolerance by restraining T-cell activation. In lupus nephritis (LN), this pathway has long been viewed as protective, based on Pdcd1-deficient mice developing lupus-like nephritis and PD-L1 fusion protein efficacy in mouse models. However, recent clinical findings reveal a paradox: PD-1⁺ T cells - especially CD8⁺ and CD4⁺ subsets - are greatly expanded in blood and kidneys of LN patients, correlating with disease activity, proteinuria, and renal decline. OBJECTIVE:To reconcile the protective and pathogenic roles of PD-1/PD-L1 signaling and propose a unifying "signal balance model" for precision immunomodulation. FINDINGS:These PD-1⁺ cells are not exhausted but exhibit an activated, clonally expanded effector phenotype (granzyme B, perforin, IFN-γ) that drives tissue injury, while PD-1⁺ Tph and Tfh cells promote autoantibody production. The biphasic nature of PD-1/PD-L1 signaling arises from T-cell subset heterogeneity, inflammatory cytokines (IL-12, IFN-α) that override inhibition, costimulatory signals, and reverse signaling through PD-L1 on renal parenchymal cells. CONCLUSIONS:We propose that the net outcome - protection versus pathogenesis - depends on the relative weights of these four determinants, further influenced by genetic background (e.g., PDCD1 polymorphisms). PD-1 agonism (rosnilimab, PD-L1-Fc, nanoparticle delivery) offers promise, but the pathogenic activity of PD-1⁺ effector T cells argues against a uniform approach. Our framework provides a basis for patient stratification, biomarker development, and combination strategies, ultimately guiding a shift from broad immunosuppression to tailored therapy in LN and informing future translational research.
Background: Natural Killer (NK) cells are essential innate immune effectors that provide constant surveillance by inducing apoptosis in infected and malignant cells primarily through degranulation. Long non-coding RNAs (lncRNAs) are regulatory transcripts (>200 nucleotides) that modulate immune cell function, yet their specific roles in NK cells remain poorly characterized despite known effects on macrophages and lymphocytes.Objective: This review aims to consolidate current knowledge on the involvement of lncRNAs in NK cell biology, focusing on their regulatory impact on NK cell development, effector functions, and interactions within the tumor microenvironment (TME).Methods: We conducted a comprehensive narrative review of the literature, synthesizing findings related to lncRNA expression and function in hematopoiesis, NK cell maturation, cytotoxicity, cytokine production, and immune checkpoint modulation.Results: Our analysis reveals that lncRNAs are emerging as critical regulators across multiple stages of NK cell biology. They influence hematopoietic differentiation, modulate NK cell development and maturation, and directly affect cytotoxic degranulation and cytokine secretion. Importantly, lncRNAs are implicated in NK cell suppression within the TME, where they modulate immune checkpoint pathways and can either enhance or diminish the anti-tumor response.Conclusion: Elucidating the specific roles of lncRNAs in NK cells is crucial for a deeper understanding of the NK cell microenvironment. These insights hold significant potential for the development of novel NK cell-based immunotherapies and the identification of new biomarkers for cancer diagnosis and prognosis.
BACKGROUND:Intracellular microbes have been detected in multiple tumors, but their impact on the tumor microenvironment of melanoma and immune regulation remains unclear. METHODS:We applied single-cell host-microbe interaction analysis to single cell RNA sequencing data from 42 melanoma samples to characterize host-microbe interactions. Multiple functional annotation approaches were integrated to assess immune and tumor cell transcriptional states associated with bacteria colonization. RESULTS:Intracellular bacteria, particularly human-colonizing bacteria were associated with distinct transcriptional alterations in the tumor immune microenvironment, characterized by increased inflammation and reduced antigen presentation signatures in myeloid cells, along with enhanced innate immune-related transcriptional patterns, whereas adaptive T cell-related immune signatures were reduced. Tumor cells also exhibited transcriptional alterations, including increased metabolic activity and extracellular matrix remodeling pathways. At the bulk transcriptomic level, colonizing bacteria-associated chronic inflammatory features were correlated with increased CD8+ T cell infiltration and improved overall survival, while also showing a potential association with responses to immunotherapy. CONCLUSIONS:Intracellular colonizing bacteria were associated with inflammation-antigen presentation imbalance in melanoma tumor microenvironment.
Background: Breast cancer (BC) remains a leading cause of cancer-related mortality because of its molecular heterogeneity, recurrence, and resistance to systemic therapies. Toll-like receptor 2 (TLR2) has emerged as a key regulator of both tumor cell signaling and the tumor microenvironment, making it a promising therapeutic target.Objective: This review summarizes the biological functions, clinical significance, and therapeutic potential of TLR2 in BC, with emphasis on its context-dependent effects across different cellular compartments.Methods: We reviewed current experimental and clinical evidence on TLR2 signaling, expression patterns, immune regulation, and therapeutic targeting in BC, integrating findings from tumor biology, immunology, and translational studies.Results: TLR2 signals primarily through the TIRAP/MYD88 pathway to activate NF-κB, MAPK, and, under specific conditions, IRF7-related pathways. Its biological effects depend on molecular subtype, ligand source, cellular context, and activation kinetics. Persistent TLR2 activation in tumor cells, cancer stem-like cells, suppressive myeloid cells, fibroblasts, and metastatic niches promotes stemness, epithelial-mesenchymal transition, metastasis, therapeutic resistance, and immune evasion. Conversely, selective activation in conventional type 1 dendritic cells and appropriately polarized macrophages enhances antigen presentation, cytotoxic T-cell priming, and antitumor immunity.Conclusions: TLR2 functions as a context-dependent immune-state switch rather than a uniformly pro-or antitumor receptor. Biomarker-guided strategies that selectively inhibit tumor-promoting TLR2 signaling while preserving or enhancing immune-activating functions may improve precision immunotherapy for BC.
Background: The tumor microenvironment (TME) is a highly complex and dynamic ecosystem composed of diverse immune cell populations. Among them, tumor-associated neutrophils (TANs) have gained increasing attention due to their dual roles in tumor progression and immunomodulation. Although neutrophils are traditionally recognized as key effector cells of the innate immune system against microbial infection, accumulating evidence highlights their functional plasticity in cancer.Methods: This review systematically summarizes and analyzes published literature focusing on TAN biology, immune regulatory mechanisms, and their impact on immune checkpoint inhibitor (ICI) therapy responses.Results: Current evidence indicates that TANs contribute to tumor initiation and progression through multiple molecular and cellular pathways. They actively participate in immune evasion within the TME and can modulate the efficacy of ICIs. Mechanistically, TANs influence anti-tumor immunity through diverse signaling networks and cellular interactions that reshape the immune landscape of tumors.Conclusion: Targeting TAN-associated pathways represents a promising strategy to improve ICI therapeutic efficacy. A deeper understanding of TAN-mediated immune regulation provides a useful framework for developing novel cancer immunotherapy approaches.
BACKGROUND:Immune reconstitution following HSCT is a complex process that strongly determines post-transplant outcomes. Delayed or impaired immune recovery increases susceptibility to opportunistic infections, viral reactivation, graft-versus-host disease, relapse, and transplant-related morbidity and mortality. OBJECTIVE:This review summarizes current evidence on the kinetics, functional recovery, and clinical significance of innate and adaptive immune reconstitution after HSCT. METHODS:A narrative review of recent literature was performed focusing on immune cell reconstitution dynamics and influencing clinical and biological factors. RESULTS:Innate immunity (neutrophils, NK cells) recovers early, providing initial defense. Adaptive immunity is delayed, driven by thymic output and peripheral T- and B-cell expansion. Regulatory T cells and γδ T cells support tolerance and graft-versus-leukemia effects. Recovery is influenced by age, conditioning, graft source, GVHD, infections, and microbiome. Numerical recovery may not equal functional immune competence. CONCLUSION:Advances in immune profiling, biomarkers, and systems immunology, along with adoptive cellular therapy and microbiome-based interventions, may enable personalized strategies to improve immune reconstitution and long-term outcomes.
BACKGROUND:Riboflavin (vitamin B2) is essential for producing flavin coenzymes (FMN and FAD) involved in redox reactions vital for immune cell functions. However, its direct effects on the immune system, particularly in human neutrophils, have been scarcely studied. METHODS:This study examined how physiologically relevant riboflavin concentrations (2.5, 25, and 50 nmol/L) affect complement activation, peripheral blood mononuclear cells (PBMC) viability and activation, and neutrophil functions such as phagocytosis, degranulation, and reactive oxygen species (ROS) production. It used pre-treatment (to simulate prior exposure) and co-treatment (to mimic ongoing supplementation). RESULTS:Riboflavin affected complement-mediated hemolysis variably depending on treatment. In PBMCs, it improved viability and regulated CD40 expression; in neutrophils, it reduced bacterial phagocytosis dose-dependently during co-treatment, with pre-treatment at 25 nmol/L inhibiting phagocytosis. Riboflavin also decreased extracellular enzyme activity, indicating suppressed degranulation. Intracellular ROS production was dose-dependently reduced during co-treatment; pre-treatment showed a biphasic response, decreasing at 2.5 and 25 nmol/L but increasing at 50 nmol/L. CONCLUSION:Riboflavin influences neutrophil functions and immune responses, highlighting the need for further research into its therapeutic potential in conditions characterized by neutrophil hyperactivation.
BACKGROUND:Ageing is a major risk factor for chronic inflammatory and immune-mediated diseases and is characterised by progressive immune dysfunction. This process, termed immunosenescence, affects both innate and adaptive immunity, resulting in reduced naïve T and B cell production, accumulation of senescent immune cells, impaired pathogen recognition, and weakened immune surveillance. These changes are accompanied by a persistent, low-grade inflammatory state known as inflammaging, which occurs even in the absence of infection and contributes to increased susceptibility to infections, poor vaccine responses, and age-related disorders. METHODS:This review integrates evidence from basic, translational, and clinical studies to elucidate the molecular and cellular mechanisms linking immunosenescence and inflammaging, with a focus on immune cell alterations and the role of senescent cells and their secretory phenotype. RESULTS:Accumulation of senescent cells and the senescence-associated secretory phenotype (SASP) play a central role in sustaining chronic inflammation and disrupting tissue homeostasis. These processes impair immune function and tissue repair, increasing vulnerability to disease. Emerging therapeutic strategies, including senolytics, senomorphics, metabolic modulators, repurposed drugs, and microbiome-targeted interventions such as postbiotics, show potential in modulating these pathways. CONCLUSION:Immunosenescence and inflammaging are closely interconnected drivers of age-related disease. Targeting senescent cells and inflammatory signalling pathways may offer promising strategies to restore immune resilience, reduce chronic inflammation, and promote healthy ageing. Further research is required to translate these approaches into clinical practice.
BACKGROUND:Conventional monoclonal antibodies generated by hybridoma technology have long been applied in disease diagnosis and treatment, yet they are constrained by inherent limitations, including epitope loss caused by chemical antigen processing and insufficient tissue penetration. Nanobodies, as single-domain antibody fragments derived from camelids and chondrichthyans, possess unique superior physicochemical characteristics such as low molecular weight, low immunogenicity, easy modification, strong tissue permeability, and precise epitope targeting. Notably, camelid-derived nanobodies exhibit high homology with human antibody subfamilies and favorable biosafety, showing promising potential for biomedical applications. METHODS:This review systematically summarizes the unique structural properties and technical advantages of nanobodies. It comprehensively sorts out the latest research progress of nanobodies in common respiratory diseases, including asthma, tuberculosis, respiratory infections, and lung cancer, and further analyzes their unique superiority in pulmonary drug delivery and clinical transformation. RESULTS:Nanobodies retain the specific antigen-binding capacity equivalent to traditional monoclonal antibodies while overcoming the defects of conventional antibody preparations. Their excellent modifiability, tissue penetration and low immunogenicity enable them to achieve accurate targeted binding in respiratory tissues. Accumulating evidence verifies the outstanding diagnostic performance and therapeutic efficacy of nanobodies in multiple respiratory disorder models, providing new technical support for pulmonary drug delivery and precise intervention of respiratory diseases. CONCLUSION:Nanobodies possess irreplaceable advantages in the diagnosis and treatment of respiratory diseases and have broad clinical translation prospects. This review clarifies the application value of nanobodies in mainstream respiratory diseases and proposes innovative strategies for the precise diagnosis and targeted treatment of respiratory disorders, laying a theoretical foundation for further clinical transformation and in-depth application of nanobody-based respiratory therapeutics.
BACKGROUND:Periodontitis involves dysregulated immunity where the NLRP3 inflammasome plays a key role, while the role of TRIM31, an E3 ubiquitin ligase, remains unknown in periodontitis. METHODS:Human gingival fibroblasts (HGFs) and macrophages were stimulated with LPS and ATP; TRIM31 was overexpressed via AAV, and NLRP3 was knocked out via CRISPR; periodontitis was induced in WT and NLRP3-KO mice treated with AAV-TRIM31; bone loss, osteoclasts, and apoptosis were assessed. RESULTS:TRIM31 was downregulated in inflammation and correlated with M2 polarization. TRIM31 overexpression protected HGFs, promoted M2 polarization, and bound to NLRP3, thereby promoting K48-linked ubiquitination and degradation. In vivo, TRIM31 reduced bone loss, osteoclasts, and apoptosis; these effects were abolished in NLRP3-KO cells and mice. CONCLUSION:TRIM31 negatively regulates periodontal inflammation via ubiquitin-dependent NLRP3 degradation.
LincRNA-Cox2 has emerged as a functionally significant long intergenic non-coding RNA in the regulation of inflammatory responses, attracting increasing attention for its diverse roles in immune signaling and gene expression control. This review begins with a brief introduction to the biological importance of inflammation and the expanding relevance of long non-coding RNAs in immunoregulation. This review then examines the broader role of lncRNAs in the inflammatory response, establishing the conceptual framework necessary to understand the specific contribution of LincRNA-Cox2. Subsequently, it addresses the discovery, biological characteristics, and expression dynamics of LincRNA-Cox2, followed by a detailed discussion of its mechanistic roles in inflammation. In addition, the review synthesizes major experimental findings derived from both in vitro studies and in vivo models, highlighting how current evidence has advanced understanding of LincRNA-Cox2-mediated immune regulation. Finally, this review discusses the major conclusions emerging from the field and outlines future directions for research, with particular emphasis on unresolved mechanistic questions and translational potential. This review aims to provide a coherent perspective on LincRNA-Cox2 as an important regulatory molecule in inflammatory biology and a promising target for future investigation.
BACKGROUND:Biochemical signals have long dominated immunology, but mechanical force is now recognized as a fundamental regulator of immune cell behavior. Immune cells sense core mechanical cues via specialized mechanosensors, and dysregulated tissue mechanics in inflammation, fibrosis and tumors disrupt normal immunity. However, previous studies lack comprehensive integration of mechanical regulation across distinct immune cell lineages. METHODS:This review systematically synthesizes advances in mechanical immunology, covering the biophysical properties of primary mechanical forces, core mechanosensor functions, mechanotransduction mechanisms across innate and adaptive immune cells, and the pathological roles and therapeutic potential of immune mechanotransduction. RESULTS:Mechanical signals regulate all critical immune cell functions through an interconnected mechanosensor network. Piezo1 mediates key processes in macrophages, neutrophils, T cells and B cells; integrins and the cytoskeleton-nuclear envelope complex transduce forces to modulate gene expression. Pathological mechanical niches drive immune dysfunction, and multiple mechanotherapeutic strategies show promising preclinical efficacy. CONCLUSION:This review establishes a comprehensive framework for immune mechanical regulation, positioning mechanical immunology as a transformative biomedical frontier. It also identifies key unresolved challenges that will guide future research and the development of precision mechanotherapies.
