Immunological Investigations最新文献

{"title":"Therapeutic Advances in Systemic Lupus Erythematosus: Targeting T Follicular Helper Cells.","authors":"Jiaxin Yang, Xue Han, Wenxi Li, Ji Yang","doi":"10.1080/08820139.2026.2647056","DOIUrl":"10.1080/08820139.2026.2647056","url":null,"abstract":"<p><strong>Background: </strong>Systemic lupus erythematosus (SLE) is a chronic systemic autoimmune disease characterized by inflammation and immune-mediated damage across multiple organ systems. Some patients with SLE respond poorly to conventional therapies. The pathogenesis of SLE is closely associated with dysregulated immune responses mediated by T follicular helper (Tfh) cells.</p><p><strong>Objective: </strong>To comprehensively review the pathogenic role of Tfh cells in SLE and summarize major therapeutic targets and representative drugs, thereby highlighting the current translational landscape of Tfh-directed strategies.</p><p><strong>Methods: </strong>Relevant studies on Tfh cells in SLE were reviewed, with emphasis on pathogenic mechanisms and therapeutic strategies targeting surface molecules, cytokines, transcription factors, and epigenetic and metabolic pathways.</p><p><strong>Results: </strong>Targeting Tfh cell-associated surface molecules, cytokines, and transcription factors has shown promising therapeutic potential. Moreover, strategies targeting epigenetic and metabolic pathways, together with innovative modalities such as bispecific antibodies and chimeric antigen receptor T (CAR-T) cell therapies, represent emerging avenues for Tfh-targeted intervention in SLE.</p><p><strong>Conclusion: </strong>Tfh cells play a central role in SLE pathogenesis and represent a promising therapeutic target. Tfh-directed strategies may support the development of precision medicine approaches based on immune profiling and combination-targeted therapies. These advances offer a theoretical foundation for overcoming current therapeutic limitations.</p>","PeriodicalId":13387,"journal":{"name":"Immunological Investigations","volume":" ","pages":"975-997"},"PeriodicalIF":2.3,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147928894","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Particulate Matter and Innate Airway Immunity: Mechanisms of Disruption and Impact on Respiratory Infections.","authors":"J Almaraz-De-Santiago, N Solís-Torres, C Escudero-Lourdes, G Méndez-Frausto, I Gonzalez-Curiel, B Rivas-Santiago, C Rivas-Santiago","doi":"10.1080/08820139.2026.2655720","DOIUrl":"10.1080/08820139.2026.2655720","url":null,"abstract":"<p><strong>Background: </strong>Air pollution is a major global public health challenge, with particulate matter (PM) as a leading environmental risk factor for increased morbidity and premature mortality worldwide. The respiratory tract is the primary interface for PM exposure, where airway epithelial cells and innate immune systems coordinate frontline host defense. Chronic PM-exposure disrupts this system, impairing airway immune homeostasis and increasing susceptibility to respiratory infections.</p><p><strong>Objective: </strong>This review aims to integrate current molecular and cellular evidence describing how PM affects airway innate immunity, focusing on its impact on host defense mechanisms and its role in increasing susceptibility to respiratory infections.</p><p><strong>Methods: </strong>A comprehensive literature review was conducted focusing on PM interactions with the respiratory tract and their effects on airway epithelial and innate immune functions, emphasizing mechanisms of immune dysregulation.</p><p><strong>Results: </strong>PM-exposure induces innate immune dysregulation characterized by oxidative imbalance, altered cytokine and chemokine signaling, reduced phagocytic capacity, and decreased production of host defense peptides, resulting in impaired epithelial barrier integrity, persistent inflammation, defective pathogen clearance, and increased susceptibility and severity of respiratory infections, including tuberculosis, bacterial pneumonia, and viral respiratory diseases such as COVID-19.</p><p><strong>Conclusion: </strong>PM is a key driver of airway innate immune dysfunction and increased susceptibility to respiratory infections by disrupting epithelial and immune defense pathways, weakening host resistance, and exacerbating disease burden. Further studies are needed to elucidate PM-immune interactions and support the development of preventive and therapeutic strategies.</p>","PeriodicalId":13387,"journal":{"name":"Immunological Investigations","volume":" ","pages":"1029-1053"},"PeriodicalIF":2.3,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147722163","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CD4-CD8-T Cell Reconstitution Combined with Acute GVHD and CMV Infection: A Robust Predictor of Overall Survival and Non-Relapse Mortality After HSCT.","authors":"Xiaoling Wang, Liang Zhao, Chao Han, Guimin Yang, Lixiao Cai","doi":"10.1080/08820139.2026.2647057","DOIUrl":"10.1080/08820139.2026.2647057","url":null,"abstract":"<p><strong>Background: </strong>Immune reconstitution (IR), acute graft-versus-host disease (aGVHD), and cytomegalovirus (CMV) infection are all crucial factors influencing the prognosis following hematopoietic stem cell transplantation (HSCT).</p><p><strong>Methods: </strong>A cohort of 116 pediatric patients undergoing HSCT was divided into two groups: those with aGVHD+CMV+ (DP group) and those without this combination (NDP group). Kaplan-Meier (KM) curves were generated to compare survival differences between the groups. Logistic regression analysis was performed to identify associations between IR and aGVHD+CMV+. Cox proportional hazards regression analysis was conducted to determine the independent risk factors affecting prognosis.</p><p><strong>Results: </strong>The prognosis of DP group was significantly worse than that of the NDP group. Notable disparities in lymphocyte subset levels were observed between the DP and NDP groups. The level of CD4-CD8-T cells showed a significant correlation with the co-occurrence of aGVHD and CMV infection. Impaired reconstitution of CD4-CD8-T cells and aGVHD+CMV+ were found to be independent risk factors for post-HSCT survival. Patients in DP group with CD4-CD8-T cell counts > 49 cells/µl (at day 90 post-HSCT) demonstrated a significantly improved prognosis.</p><p><strong>Conclusions: </strong>Elevated CD4-CD8-T cell counts may mitigate the adverse effects of aGVHD and CMV infection on HSCT outcomes, suggesting their potential as a prognostic biomarker.</p>","PeriodicalId":13387,"journal":{"name":"Immunological Investigations","volume":" ","pages":"889-907"},"PeriodicalIF":2.3,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147490971","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacological Modulation of Immunosenescence and Inflammaging: Senolytics, Senomorphics, and Emerging Therapies.","authors":"Bhavya R, Rajendra Sandur V","doi":"10.1080/08820139.2026.2695165","DOIUrl":"https://doi.org/10.1080/08820139.2026.2695165","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":13387,"journal":{"name":"Immunological Investigations","volume":" ","pages":"1-26"},"PeriodicalIF":2.3,"publicationDate":"2026-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148351868","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Riboflavin Modulates Complement Activation, Immune Cell Viability and Activation, and Neutrophil Microbicidal Functions <i>in Vitro</i>.","authors":"Honorio Torres-Aguilar, Alexia Almaraz-Arreortua, Salma Luis-Ordóñez, Alondra De Gaona-García, Yadira Ivonne Jimenez-Lopez, Gisela Fuentes-Mascorro, Sergio Roberto Aguilar-Ruiz, María de Los Ángeles Romero-Tlalolini","doi":"10.1080/08820139.2026.2693030","DOIUrl":"https://doi.org/10.1080/08820139.2026.2693030","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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).</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>Riboflavin influences neutrophil functions and immune responses, highlighting the need for further research into its therapeutic potential in conditions characterized by neutrophil hyperactivation.</p>","PeriodicalId":13387,"journal":{"name":"Immunological Investigations","volume":" ","pages":"1-20"},"PeriodicalIF":2.3,"publicationDate":"2026-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148351833","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nanoantibodies: A Review of Diagnostic and Therapeutic Applications in Respiratory Diseases.","authors":"Na Zhang, Huiling Lü, Kaili Shi, Runle Li, Feng Tang","doi":"10.1080/08820139.2026.2686756","DOIUrl":"https://doi.org/10.1080/08820139.2026.2686756","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":13387,"journal":{"name":"Immunological Investigations","volume":" ","pages":"1-22"},"PeriodicalIF":2.3,"publicationDate":"2026-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148316936","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TRIM31: A Novel Guardian Against Periodontal Inflammation via Modulation of NLRP3 Inflammasome and Macrophage Polarization.","authors":"Xiaolu Zhang, Dazhuang Lu, Lijia Lin, Weijuan Qi, Shan He","doi":"10.1080/08820139.2026.2680504","DOIUrl":"10.1080/08820139.2026.2680504","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>TRIM31 negatively regulates periodontal inflammation via ubiquitin-dependent NLRP3 degradation.</p>","PeriodicalId":13387,"journal":{"name":"Immunological Investigations","volume":" ","pages":"1-21"},"PeriodicalIF":2.3,"publicationDate":"2026-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148294835","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"LincRNA-Cox2 in Inflammation: Regulatory Networks, Experimental Insights, and Future Directions.","authors":"Xing Huang, Zhaoqun Yang","doi":"10.1080/08820139.2026.2687809","DOIUrl":"https://doi.org/10.1080/08820139.2026.2687809","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":13387,"journal":{"name":"Immunological Investigations","volume":" ","pages":"1-26"},"PeriodicalIF":2.3,"publicationDate":"2026-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148271335","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanical Regulation of the Immune System: From Sensory Mechanisms to Disease Pathogenesis.","authors":"Yubo He, Minghui Zhang, Sheng Xia","doi":"10.1080/08820139.2026.2685000","DOIUrl":"https://doi.org/10.1080/08820139.2026.2685000","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":13387,"journal":{"name":"Immunological Investigations","volume":" ","pages":"1-35"},"PeriodicalIF":2.4,"publicationDate":"2026-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148251506","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"IL-12 Family Cytokines as Key Regulators of Systemic Autoimmunity: Emerging Therapeutic Insights.","authors":"Yang Chao, Xing Huang","doi":"10.1080/08820139.2026.2680484","DOIUrl":"https://doi.org/10.1080/08820139.2026.2680484","url":null,"abstract":"<p><p>The interleukin-12 (IL-12) family of cytokines has emerged as an area of growing interest in immunology and systemic autoimmune disease (SAD) research. As a group of structurally related cytokines with diverse yet interconnected functions, these molecules occupy an important position at the interface of innate and adaptive immunity. Their biological complexity, together with their broad immunologic relevance, has made them a prominent subject of investigation in recent years. Within SADs, the IL-12 family has attracted increasing attention because of its wide association with immune-mediated processes across multiple clinical settings. From systemic lupus erythematosus and rheumatoid arthritis to systemic sclerosis and Sjögren's syndrome, interest in this cytokine family reflects a broader effort to better understand the molecular networks that shape systemic immune dysregulation. In this regard, current knowledge continues to expand, linking cytokine biology with evolving concepts in disease characterization and clinical interpretation. Against this background, the aim of this article is to provide an integrated overview of the IL-12 family in systemic autoimmunity, while highlighting its potential clinical utility and emphasizing its promise as a relevant tool in the future management of SADs.</p>","PeriodicalId":13387,"journal":{"name":"Immunological Investigations","volume":" ","pages":"1-46"},"PeriodicalIF":2.4,"publicationDate":"2026-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148149604","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}