Immunological Investigations最新文献

Background: Organ transplantation faces challenges of chronic rejection and infection due to immunosuppression. Inducing long-term immune tolerance is a key goal, with anti-CD45RB antibody being a studied target for decades.

Methods: This review examines its mechanisms-modulating T cells (e.g.promoting Tregs), B cells, and cytokines-and efficacy across transplantation models (e.g.pancreatic, cardiac, cutaneous), including combination therapies.

Conclusions: Efficacy varies by model: monotherapy induced tolerance in certain islet transplants but not skin grafts. Combination with agents like anti-CD40L or rapamycin significantly prolonged graft survival (e.g.to 100% in heart transplants). Dosage, timing, and recipient immune status influence outcomes, with Treg involvement as a common mechanism.

Future directions: Further research should explore synergies with clinical immunosuppressants and mechanisms in large animal xenografts to advance clinical translation.

Background: The interaction between the immune system and fungi has long intrigued researchers, as fungi are among the most common organisms encountered by humans. Myeloid-derived suppressor cells (MDSCs) are specialized immune cells that play a key role in modulating immune responses during fungal infections by inhibiting T-cell activity.

Objectives: This review aims to investigate the mechanisms by which MDSCs influence fungal infections and to explore their potential as therapeutic targets.

Methods: A comprehensive review of existing studies examining MDSC activity in various fungal infections was conducted. Comparative analysis focused on the protective versus non-protective effects of MDSCs across different fungal species.

Results: MDSCs suppress pro-inflammatory T-cell responses, leading to two contrasting outcomes. On one hand, this suppression mitigates disease progression by reducing harmful inflammation. On the other, it can enhance fungal survival by preventing T-cell-mediated damage. Protective effects of MDSCs have been observed in Candida albicans infections, whereas non-protective or detrimental effects have been reported in infections caused by Candida tropicalis, Paracoccidioides, Aspergillus fumigatus, Cryptococcus neoformans, Malassezia, and Mucor species.

Conclusions: MDSCs play a dual role in fungal infections, balancing protective immune regulation with facilitation of fungal persistence. Understanding their mechanisms offers promising avenues for the development of targeted immunotherapies against fungal pathogens.

Introduction: The immunosuppressive microenvironment of hepatocellular carcinoma (HCC) is shaped by multiple oncogenic pathways, but howosteopontin (OPN), a molecule frequently overexpressed in HCC, regulates anti-tumor immunity remains unclear.

Methods: To define the mechanism by which OPN modulates the HCC immune microenvironment, with a focus on its regulation of CD155 and its impact on CD8⁺ T-cell - mediated anti-tumor responses.

Results: We identified that OPN activates the p65/NF-κB - c-Myc/CD155 signaling axis, leading to robust upregulation of CD155 and impaired intratumoral CD8⁺ T-cell infiltration and effector activity. These immunosuppressive effects occurred independently of changes in tumor stemness markers or Treg accumulation. Genetic suppression of p65 abrogated OPN-induced CD155 expression and mitigated tumor progression in vivo, demonstrating the pathway's functional requirement.

Discussion: OPN drives HCC progression by suppressing CD8⁺ T-cell immunity through the NF-κB (p65)/c-Myc/CD155 axis. Targeting this pathway may enhance anti-tumor immunity and represents a promising therapeutic strategy for HCC.

Background: Obesity-induced metabolic stress impairs the efficacy of immune checkpoint blockade (ICB) therapy, but the mechanisms linking a high-fat diet (HFD) to immune suppression remain unclear.

Objective: To investigate how HFD-induced metabolic changes modulate the tumor immune microenvironment through the STAT3/CD155 axis.

Methods: Murine colorectal cancer models using control, CD155-overexpressing (CD155 OE), and STAT3 knockdown CT26 cells were established under normal or HFD conditions with anti - PD-L1 treatment. Tumor growth, immune infiltration, and gene expression were analyzed by flow cytometry, Western blotting, and chromatin immunoprecipitation.

Results: HFD impaired anti - PD-L1 efficacy and accelerated tumor growth. Mechanistically, HFD promoted STAT3 nuclear translocation and CD155 upregulation, reducing CD8⁺ T cell infiltration and enhancing regulatory T cell accumulation. Chromatin immunoprecipitation confirmed direct STAT3 binding to the CD155 promoter, while STAT3 knockdown reversed these effects and restored antitumor immunity in HFD-fed mice.

Conclusion: HFD-induced metabolic stress drives immune evasion via the STAT3/CD155 axis. Targeting this pathway may improve ICB efficacy in obesity-related cancers.

Background: The gut microbiota plays an important role in systemic immune homeostasis and is increasingly implicated in autoimmune thyroid disease (AITD). Evidence suggests that gut dysbiosis, impaired intestinal barrier function, and altered microbial metabolites particularly short-chain fatty acids contribute to immune imbalance along the gut-thyroid axis. Although molecular mimicry between microbial and thyroid antigens has been proposed, current human evidence remains associative rather than causal.

Methods: This review synthesized current observational, translational, and preclinical studies evaluating microbial composition, barrier integrity, microbial metabolites, and immune pathways relevant to AITD. Mechanistic insights into T-lymphocyte regulation and microbial-host interactions were integrated with emerging interventional data.

Results: Gut dysbiosis in AITD is linked to reduced regulatory T-lymphocytes, expansion of Th17 cells, increased intestinal permeability, and the loss of short-chain-fatty-acid-producing taxa. Observational studies consistently report disease-associated taxonomic alterations, while preclinical models support causal pathways through barrier disruption and microbiota-driven immune activation. Early interventional approaches such as high-fiber dietary patterns, probiotics, prebiotics, and experimental fecal microbiota transplantation show modest reductions in thyroid autoantibodies in small trials, though effects are strain-specific, short-term, and not disease-modifying.

Conclusion: Despite largely associative human evidence, converging mechanistic findings highlight the gut microbiota as a modifiable contributor to thyroid autoimmunity. Future priorities include clarifying causality, identifying keystone microbial taxa and metabolites, and establishing standardized interventional frameworks to facilitate translation into endocrine practice.

Background: Cardiomyopathies contribute substantially to heart failure, arrhythmias, and sudden cardiac death. Innate immune activation-particularly via Toll-like receptors (TLRs)-is increasingly recognized as a driver of pathological cardiac remodeling.

Objective: To evaluate how TLR expression and downstream signaling pathways (MyD88 and TRIF) shape distinct cardiomyopathy phenotypes and to assess therapeutic strategies targeting these mechanisms.

Methods: Evidence from studies of ischemic, viral, septic, diabetic, drug-induced, hypertrophic, and obesity-associated cardiomyopathies was surveyed to determine the roles of TLR subtypes and the impact of modulating their signaling pathways.

Results: Activation of TLR2, TLR3, TLR4, TLR7, and TLR9 consistently amplifies myocardial inflammation, fibrosis, and functional decline. However, context-dependent protective effects in certain settings highlight the complexity of uniformly suppressing TLR activity. Preclinical investigations demonstrate favorable outcomes from selective pathway modulation, including TLR4 antagonists (such as TAK-242 and eritoran), MyD88 pathway inhibitors, and nucleic-acid-directed TLR9 strategies.

Conclusions: Targeting TLR signaling has strong potential to limit inflammation, curb fibrotic remodeling, and preserve cardiac function across diverse cardiomyopathies. The most promising therapeutic direction involves developing subtype-specific and cell- or pathway-targeted interventions, supported by translational research to bridge preclinical findings with clinical application.

Background: Asthma and chronic obstructive pulmonary disease (COPD) - two common airway diseases - have drawn greater attention lately because of their increasing occurrence and mortality rates. The main inflammatory types - type 2 and non-type 2, which include type 1 and type 3 inflammation - are distinguished by the presence of discrete immune cells, that coordinate the recruitment and activation of inflammatory cells, resulting in various pathological presentations, clinical symptoms, therapeutic responses, and prognoses. Despite significant differences, COPD and asthma share many inflammatory commonalities. In recent years, the type 2 inflammatory phenotype in COPD has steadily emerged as the focus of COPD research. Understanding the differences between COPD and asthma with type 2 inflammatory phenotypes is critical for designing individualized treatment strategies.

Methods and results: This review systematically searched for Chinese and English literature on COPD and asthma in the field of type 2 inflammation, and conducted a comprehensive review and analysis of the relevant content. It explored the similarities and differences between type 2 inflammatory phenotypes in COPD and asthma, with particular emphasis on their inflammatory mechanisms, clinical features, biomarkers, therapeutic targets, and treatment responses.

Conclusion: This review investigates the similarities and differences between type 2 inflammatory phenotypes in COPD and asthma, with the aim of better addressing their diversities, gain deeper insights into their underlying cellular and molecular mechanisms, develop novel therapies in unmet areas, explore more effective treatment directions, reduce the disease burden, and enhance patient outcomes.

Background: Rheumatoid arthritis (RA) is a chronic autoimmune manifestation characterized by persistent chronic inflammation and joint damage. B cells play pivotal roles in the immune system, recognize antigens, and facilitate subsequent immune responses. Recent advancements in single-cell resolution techniques and immunogenomics have provided unprecedented insights into deciphering the complex mechanisms underlying B-cell dysregulation in RA.

Methods and results: This review article aims to articulate the current knowledge on how aberrant B cell activation and BCR signalling contribute to the development and perpetuation of self-reactive B cells in RA. Furthermore, this article explores immunogenomic insights that have shed light on the impaired B cell expansion and genetic variations in B cell-specific genes observed in RA patients, unveiling new layers of complexity in the underlying mechanisms driving autoimmune processes.

Conclusion: This article focused on abberant B cell activation and immunogenomics aspects of B cells in rheumatoid arthritis. Precise identification of abberant BCR signalling pathways, abberant genetic variats and extensive abnormalities in DNA can provide detailed insights to direct structural and therapeutic interventions against autoimmune and hypersensitive disorders.

Background: Periodontal disease is a prevalent chronic inflammatory condition of the tooth-supporting tissues characterized by progressive loss of connective attachment and alveolar bone. The IL-12 cytokine family-comprising IL-12, IL-23, IL-27, and IL-35-plays key yet divergent roles in shaping periodontal immune responses through heterodimeric subunits and distinct JAK-STAT signaling pathways. These cytokines differentially regulate inflammation, microbial interactions, and bone resorption.

Methods: This review integrates experimental and clinical evidence assessing IL-12 family members in saliva, gingival crevicular fluid, and periodontal tissues. Studies examining cytokine expression profiles, their correlation with disease activity, microbial dysbiosis, and treatment response were analyzed. Mechanistic data elucidating how IL-12 family signaling modulates inflammatory cascades and osteoclastogenic pathways were also evaluated.

Results: IL-12 and IL-23 predominantly amplify pro-inflammatory responses by promoting Th1/Th17 polarization, enhancing neutrophil recruitment, and driving osteoclastogenesis, thereby linking dysbiotic biofilms to tissue destruction. In contrast, IL-27 and IL-35 exhibit context-dependent immunoregulatory properties, inducing IL-10-mediated anti-inflammatory signaling and expanding regulatory T and B cell compartments to support the resolution of inflammation. Across clinical samples, cytokine levels consistently reflect disease severity and demonstrate modulation following periodontal therapy, underscoring their potential as adjunctive biomarkers.

Conclusion: Members of the IL-12 cytokine family exert both pathogenic and protective influences in periodontal disease. Therapeutic strategies that suppress IL-12/IL-23-driven inflammation while augmenting IL-27/IL-35-mediated regulation show promise as host-modulatory approaches in periodontal treatment. A deeper understanding of these immunologic dynamics may advance precision-based periodontal therapies.

Background: Treating traumatic spinal cord injury (SCI) requires mitigating microglia-mediated inflammation and nerve damage. Phillyrin (phi) shows neuroprotective potential, but its effects on SCI are unknown. We investigated phi's impact on microglial activation, inflammation, neuronal apoptosis, and pyroptosis in mice after SCI.

Methods: A mouse contusion SCI model was used to assess phi efficacy. Functional recovery was assessed with BBB and LSS scales. Histological and TUNEL staining were used to evaluate tissue damage and neuronal survival. Microglial phenotypes, inflammation, pyroptosis, oxidative stress and Nrf2/HO-1 pathway were analyzed.

Results: Phi treatment accelerated motor function recovery, improved tissue pathology, increased live cells, and reduced apoptosis. Phi treatment showed a decrease in the proportion of M1 pro-inflammatory microglia characterized by iNOS, an increase in the proportion of M2 anti-inflammatory microglia characterized by Arg1 and a reduction in inflammatory factors. Phi enhanced Nrf2 expression in neurons and microglia, activated HO-1 and NQO1 expression, weaken oxidative stress, and improved pyroptosis.

Conclusion: Phi alleviates SCI by activating the Nrf2/HO-1 pathway, suppressing microglial activation-mediated neuroinflammation, neuronal apoptosis, oxidative stress and pyroptosis. This study provides the first evidence of the therapeutic effect of phi on traumatic SCI, providing theoretical support for its future clinical application in SCI.