International Reviews of Immunology最新文献

{"title":"Phagosomal escape and sabotage: The role of ESX-1 and PDIMs in <i>Mycobacterium tuberculosis</i> pathogenesis.","authors":"Mohd Shariq, Farhan Ahmed, Onaiza Ansari, Anam Mursaleen, Javaid Ahmad Sheikh","doi":"10.1080/08830185.2025.2531828","DOIUrl":"https://doi.org/10.1080/08830185.2025.2531828","url":null,"abstract":"<p><p><i>Mycobacterium tuberculosis</i> (<i>M. tb</i>) employs diverse virulence factors to evade immune defenses and persist intracellularly. The ESAT-6 secretion system-1 (ESX-1) type VII secretion system (T7SS) releases EsxA, EspA, and EspB, inducing phagosomal rupture and cytosolic access while triggering host defenses, including galectin recruitment and stress granule formation. To counteract host responses, <i>M. tb</i> utilizes phthiocerol dimycocerosates (PDIMs) to inhibit autophagy and LC3-associated phagocytosis (LAP) by suppressing NADPH oxidase (NOX2) recruitment and reactive oxygen species (ROS) production. Additionally, CspA blocks LC3 lipidation, impairing LAP activation and phagosome maturation. EsxG and EsxH interfere with ESCRT-mediated phagosomal repair, further enhancing intracellular survival. Cytosolic <i>M. tb</i> is ubiquitinated by host E3 ligases, marking it for selective autophagy (xenophagy), yet <i>M. tb</i> evades degradation by manipulating autophagic flux. Simultaneously, <i>M. tb</i>-derived DNA activates the cyclic GMP-AMP synthase-stimulator of interferon response cGAMP interactor 1 (CGAS-STING1) axis, leading to type I interferon (IFN) signaling and inflammasome activation, which drive IL-1B and IL-18 secretion, necrosis, and pyroptosis, facilitating bacterial dissemination. Additionally, exosomes released during infection disseminate bacterial components, modulating immune responses systemically. This review uniquely integrates current findings on the coordinated actions of ESX-1 T7SS and PDIMs in mediating phagosomal rupture and immune evasion, offering a unified framework for understanding <i>M. tb</i>'s intracellular survival strategies. By bridging lipid- and protein-mediated virulence mechanisms and their impact on host autophagy, inflammasome activation, and phagosomal repair pathways, this work provides novel insights into therapeutic targets aimed at restoring host immune function.</p>","PeriodicalId":14333,"journal":{"name":"International Reviews of Immunology","volume":" ","pages":"1-27"},"PeriodicalIF":4.3,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144659168","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":"Immune cells in liver regeneration: Current evidence and potential clinical targets.","authors":"Hollie F Moore, Saba Usmani, Saied Froghi, Hasan Rashidi, Alberto Quaglia, Barry Fuller, Brian R Davidson","doi":"10.1080/08830185.2025.2531820","DOIUrl":"https://doi.org/10.1080/08830185.2025.2531820","url":null,"abstract":"<p><p>The livers' ability to regenerate after injury has attracted the investigation of possible therapeutic targets for liver disease. Cells of the immune system are considered fundamental for the initiation, propagation, and termination of liver regeneration as they produce essential signaling molecules, such as cytokines, chemokines, and growth factors. Previous evidence mainly focused on macrophage involvement in liver regeneration, namely Kupffer cells which secrete mitogenic cytokines. However, recent evidence has implicated other immune cell subsets in liver regeneration including platelets, the complement system, dendritic cells, granulocytes, and innate and adaptive lymphocytes. The concurrent function of different immune cell subsets highlights functional redundancies between immune cells and the temporospatial dynamics of liver regeneration. In this review, we discuss our understanding of the role of immune cells in liver regeneration, recent advances and cellular targets identified for clinical therapy over the past decade.</p>","PeriodicalId":14333,"journal":{"name":"International Reviews of Immunology","volume":" ","pages":"1-40"},"PeriodicalIF":4.3,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144626301","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":"B cell antigens: A key to optimizing CAR-T cell therapy.","authors":"Purva Khodke, Dhananjay Hasurkar, Aakanksha Upadhyay, Aditi Shedge, Rhea Sippy, Bajarang Vasant Kumbhar","doi":"10.1080/08830185.2025.2515839","DOIUrl":"10.1080/08830185.2025.2515839","url":null,"abstract":"<p><p>B-cells are vital immune cells that differentiate into plasma cells to produce antibodies targeting specific antigens. They also act as Antigen Presenting Cells, displaying processed antigens on Major Histocompatibility Complex class-II molecules to activate helper T-cells. This process triggers immune response and memory development. B-cells have surface antigens crucial for their function, which are often overexpressed in B cell cancers, making them targets for therapies like Chimeric Antigen Receptor (CAR) T-cell therapy. However, the choice of antigen is crucial. Tumor associated antigens are common but can cause off-target effects, while tumor specific antigens are more specific but less common. Furthermore, the precise epitope on the antigen recognized by the CAR-T cells significantly influences activation, which can also depend on the epitope's distance from the B-cell membrane. To facilitate the identification of extracellular regions of tumor antigens for CAR interactions, this review models tumor antigen structures embedded in the lipid bilayer, analyzing their roles and functions. Specifically, the characterization of B-cell surface antigens, encompassing their structural features and their potential as targets for CAR-T therapy are discussed. Each antigen is meticulously examined to gain insights into their specific roles within B cell biology and their potential as therapeutic targets. In conclusion, this review highlights the importance of understanding B cell antigens for the development of effective CAR-T cell therapies. The insights into antigen structures and functions presented here can guide the selection of optimal targets and the design of CAR-T cells to combat B cell malignancies effectively.</p>","PeriodicalId":14333,"journal":{"name":"International Reviews of Immunology","volume":" ","pages":"1-28"},"PeriodicalIF":4.3,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144333114","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":"Immunological insights into role of Th9 and Treg cell homeostasis and cytokines dynamics in the progression of diabetic nephropathy.","authors":"Manoj Khokhar, Purvi Purohit, Ashita Gadwal, Nitin Kumar Bajpai, Ravindra Kumar Shukla","doi":"10.1080/08830185.2025.2515836","DOIUrl":"https://doi.org/10.1080/08830185.2025.2515836","url":null,"abstract":"<p><strong>Background: </strong>T cells play a crucial role in immune responses and are involved in chronic diseases such as Type 2 Diabetes Mellitus (T2DM) and its complications, including Diabetic Nephropathy (DN). Among these, regulatory T cells (Treg) act as key regulators, while T helper 9 (Th9) cells, which produce IL-9, are essential in maintaining immune balance.</p><p><strong>Methods: </strong>The study included 145 participants divided into four groups: T2DM with nephropathy (35), T2DM without nephropathy (35), non-diabetic chronic kidney disease (ND-CKD) (35), and healthy controls (35). Various assessments were conducted, including anthropometric measurements, biochemical analyses, gene expression analysis was performed using RT-qPCR to profile mRNA and miRNA expression levels, flow cytometry (immune cell populations), and cytokine analysis by ELISA. Statistical analyses were carried out using SPSS, jamovi, Orange Data Mining, and Excel, ensuring robust evaluation and interpretation of the data.</p><p><strong>Results: </strong>Th9 cells correlated with IL-9 (<i>r</i> = 0.72, <i>p</i> < 0.01), and Treg cells with IL-10 (<i>r</i> = 0.68, <i>p</i> < 0.01). The Th9/Treg ratio significantly increased across groups (χ² = 14.8, <i>p</i> < 0.001), with notable differences between HC and T2DM (<i>p</i> = 0.009) and HC and DN (<i>p</i> < 0.001). IL-9 (AUC = 0.880) and Th9/Treg ratio (AUC = 0.762) showed potential as DN diagnostic markers. PTEN levels were reduced in DN and ND-CKD (<i>p</i> < 0.001, <i>p</i> = 0.017), while MMP2, hsa-miR-21-5p, and hsa-miR-181b-5p were elevated in disease groups (all <i>p</i> < 0.001), correlating with renal markers. COL4A4 was higher in DN vs. HC (<i>p</i> = 0.004), with PTEN downregulation linked to immune imbalance and fibrosis.</p><p><strong>Conclusion: </strong>Our study unveils immune cell and cytokine intricacies in DN. The high Th9/Treg ratio in T2DM and DN suggests immune tolerance loss, potentially influencing DN development. IL-9 and IL-10 display diagnostic potential. The Th9/Treg ratio and IL-9 serves as a discriminative diagnostic marker, particularly in DN. These insights offer avenues for early DN diagnosis and management.</p>","PeriodicalId":14333,"journal":{"name":"International Reviews of Immunology","volume":" ","pages":"1-25"},"PeriodicalIF":4.3,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144274790","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":"Recurrent respiratory papillomatosis: Immunological mechanisms involved in recurrence.","authors":"Katya Karen López-Aguilar, María Eugenia Vargas-Camaño, Fernando Lozano-Patiño, María Isabel Castrejón Vázquez","doi":"10.1080/08830185.2024.2425428","DOIUrl":"10.1080/08830185.2024.2425428","url":null,"abstract":"<p><p>Recurrent respiratory papillomatosis is a benign neoplastic pathology in children, young people, and adults. It causes a significant deterioration in the quality of life, with symptoms typically referred to as dysphonia and hoarseness. This disease, with variable clinical courses ranging from spontaneous resolution to dissemination of the lower airway or airway obstruction that puts the individual's life at risk, characteristically requires multiple surgical interventions. Therapy with adjuvant drugs does not yet prove the effectiveness necessary to limit the recurrence and need for surgical reoperation in this condition. The review aimed to synthesize the immunopathogenic mechanisms of relapse in recurrent respiratory papillomatosis published in the current literature and the immunological implication of risk factors and treatment.</p>","PeriodicalId":14333,"journal":{"name":"International Reviews of Immunology","volume":" ","pages":"113-126"},"PeriodicalIF":4.3,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142604076","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":"Boosting antitumor immunity in breast cancers: Potential of adjuvants, drugs, and nanocarriers.","authors":"Ping Chen, Lei Ren, Youwei Guo, Yan Sun","doi":"10.1080/08830185.2024.2432499","DOIUrl":"10.1080/08830185.2024.2432499","url":null,"abstract":"<p><p>Despite advancements in breast cancer treatment, therapeutic resistance, and tumor recurrence continue to pose formidable challenges. Therefore, a deep knowledge of the intricate interplay between the tumor and the immune system is necessary. In the pursuit of combating breast cancer, the awakening of antitumor immunity has been proposed as a compelling avenue. Tumor stroma in breast cancers contains multiple stromal and immune cells that impact the resistance to therapy and also the expansion of malignant cells. Activating or repressing these stromal and immune cells, as well as their secretions can be proposed for exhausting resistance mechanisms and repressing tumor growth. NK cells and T lymphocytes are the prominent components of breast tumor immunity that can be triggered by adjuvants for eradicating malignant cells. However, stromal cells like endothelial and fibroblast cells, as well as some immune suppressive cells, consisting of premature myeloid cells, and some subsets of macrophages and CD4+ T lymphocytes, can dampen antitumor immunity in favor of breast tumor growth and therapy resistance. This review article aims to research the prospect of harnessing the power of drugs, adjuvants, and nanoparticles in awakening the immune reactions against breast malignant cells. By investigating the immunomodulatory properties of pharmacological agents and the synergistic effects of adjuvants, this review seeks to uncover the mechanisms through which antitumor immunity can be triggered. Moreover, the current review delineates the challenges and opportunities in the translational journey from bench to bedside.</p>","PeriodicalId":14333,"journal":{"name":"International Reviews of Immunology","volume":" ","pages":"141-164"},"PeriodicalIF":4.3,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142750878","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":"Asthma research in mice: An overview of current models and their methodological variability.","authors":"Yan-Jiao Chen, Cai-Tao Chen, Gabriel Shimizu Bassi, Yong-Qing Yang","doi":"10.1080/08830185.2024.2431507","DOIUrl":"10.1080/08830185.2024.2431507","url":null,"abstract":"<p><p>Studies in murine experimental models have made significant contributions to the understanding of asthma pathophysiology and the discovery of innovative therapeutic approaches. Nonetheless, there is a plethora of options available for selecting mouse strains, sensitization methods, challenge routes and doses, as well as approaches to evaluating host response in murine asthma model protocols. Due to the diversity of models employed, comparing results across different studies proves exceedingly challenging. The study conducted a search of pertinent PubMed articles from 2022 to April 15th, 2024. After relevant publications had been selected, the characteristics of each study were extracted, including animal strains, animal sex, sensitization methods, challenge methods, and reported outcome measures. The modeling parameters of Ovalbumin (OVA)-induced asthma model, and House Dust Mite-induced asthma model were analyzed. Additionally, we extracted data on the dose of OVA sensitization, alum administration, challenge OVA dose, and alum/sensitization OVA ratio from seven included studies. Subsequently, we conducted an analysis to determine the correlation between each of these factors and the lung resistance index (RI). This study presents an overview of the current mouse asthma models, offering valuable methodological guidance for researchers. Furthermore, this study highlights that certain parameters like sensitization dose, challenge dose, and so on, exert specific effects on the asthma lung resistance. However, there is a lack of standardized criteria and guidelines in this regard. The effects and underlying mechanisms of parameters on asthma responses remain unclear, necessitating further investigation into model parameters.</p>","PeriodicalId":14333,"journal":{"name":"International Reviews of Immunology","volume":" ","pages":"127-140"},"PeriodicalIF":4.3,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142800798","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":"Solute carrier family 15 member 4, an emerging therapeutic target for systemic lupus erythematosus.","authors":"Lai Wang, Jiao Jiang, Haoyuan Yin, Xiaoke Wang, Qilin Li, Hongyang Li, Junhui Wu, Qianjin Lu","doi":"10.1080/08830185.2025.2491644","DOIUrl":"https://doi.org/10.1080/08830185.2025.2491644","url":null,"abstract":"<p><p>Systemic lupus erythematosus (SLE) is a prototypical autoimmune disease characterized by excessive production of type I interferons (IFNs) and autoantibodies with limited effective clinical treatments. Solute carrier family 15 member 4 (SLC15A4), a proton-coupled oligopeptide transporter, facilitates the transmembrane transport of L-histidine and some di- and tripeptides from the lysosome to the cytosol. A growing body of evidence has elucidated the critical role of SLC15A4 in pathogenesis and disease progression of SLE. Genome-wide association studies have identified SLC15A4 as a new susceptibility locus of SLE. Further mechanistical studies have demonstrated that SLC15A4 involves in the production of type I IFNs in plasmacytoid dendritic cells (pDCs) and its necessity in B cells for autoantibody production in lupus models. These studies strongly support the potential of SLC15A4 as a promising therapeutic target for SLE. This review aims to summarize recent advances in understanding the role of SLC15A4 in disease progression of SLE and the development of SLC15A4-targeted inhibitors as well as discuss its potential as a target for SLE treatment.</p>","PeriodicalId":14333,"journal":{"name":"International Reviews of Immunology","volume":" ","pages":"1-15"},"PeriodicalIF":4.3,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143965424","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":"Unraveling the significance of innate inflammation in vascular disease.","authors":"Alice Valeria Wiyono, Azizah Puspitasari Ardinal, Pradana Pratomo Raharjo","doi":"10.1080/08830185.2025.2489346","DOIUrl":"https://doi.org/10.1080/08830185.2025.2489346","url":null,"abstract":"<p><p>Atheroma formation is initiated by the activation of endothelial and smooth muscle cells, as well as immune cells, including neutrophils, lymphocytes, monocytes, macrophages, and dendritic cells. Monocytes, macrophages, and neutrophils are the innate immune cells that provide a rapid initial line of defence against vascular disease. These cells have a short lifespan and cannot retain memories, making them potential therapeutic targets for the inflammatory process associated with atherosclerosis. In addition, macrophages comprise the majority of vessel wall infiltrates and are, therefore, implicated in all stages of atherosclerosis progression. Neutrophils are the most common type of leukocyte found in circulation, and their high levels of matrix-degrading protease explain their significance in fibrous cap destabilization. However, the activation of immune cells becomes more complex by various microenvironmental stimuli and cytokines, which ultimately transform immune cells into their pro-inflammatory state. Different types of macrophage subsets with distinct functions in inflammation, such as M1 macrophages, cause an increase in pro-inflammatory cytokines and produce reactive oxygen species and nitric oxide, further worsening the disease. This review aims to shed light on immune-mediated inflammation in cardiovascular disease by focusing on the role of macrophage subsets in vascular inflammation and plaque stability, as well as the interaction between neutrophils and monocyte-macrophages.</p>","PeriodicalId":14333,"journal":{"name":"International Reviews of Immunology","volume":" ","pages":"1-16"},"PeriodicalIF":4.3,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144012193","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":"Innate lymphoid cells, immune functional dynamics, epithelial parallels, and therapeutic frontiers in infections.","authors":"Wafa Nouari, Mourad Aribi","doi":"10.1080/08830185.2025.2490233","DOIUrl":"https://doi.org/10.1080/08830185.2025.2490233","url":null,"abstract":"<p><p>Innate lymphoid cells (ILCs) have emerged as pivotal players in the field of immunology, expanding our understanding of innate immunity beyond conventional paradigms. This comprehensive review delves into the multifaceted world of ILCs, beginning with their serendipitous discovery and traversing their ontogeny and heterogeneity. We explore the distinct subsets of ILCs unraveling their intriguing plasticity, which adds a layer of complexity to their functional repertoire. As we journey through the functional activities of ILCs, we address their role in immune responses against various infections, categorizing their interactions with helminthic parasites, bacterial pathogens, fungal infections, and viral invaders. Notably, this review offers a detailed examination of ILCs in the context of specific infections, such as <i>Mycobacterium tuberculosis</i>, <i>Citrobacter rodentium</i>, <i>Clostridium difficile</i>, <i>Salmonella typhimurium</i>, <i>Helicobacter pylori</i>, <i>Listeria monocytogenes</i>, <i>Staphylococcus aureus</i>, <i>Pseudomonas aeruginosa</i>, <i>Influenza virus</i>, Cytomegalovirus, Herpes simplex virus, and severe acute respiratory syndrome coronavirus 2. This selection aimed for a comprehensive exploration of ILCs in various infectious contexts, opting for microorganisms based on extensive research findings rather than considerations of virulence or emergence. Furthermore, we raise intriguing questions about the potential immune functional resemblances between ILCs and epithelial cells, shedding light on their interconnectedness within the mucosal microenvironment. The review culminates in a critical assessment of the therapeutic prospects of targeting ILCs during infection, emphasizing their promise as novel immunotherapeutic targets. Nevertheless, due to their recent discovery and evolving understanding, effectively manipulating ILCs is challenging. Ensuring specificity and safety while evaluating long-term effects in clinical settings will be crucial.</p>","PeriodicalId":14333,"journal":{"name":"International Reviews of Immunology","volume":" ","pages":"1-28"},"PeriodicalIF":4.3,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143966871","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}