International Reviews of Immunology最新文献

{"title":"The clinical and immunological paradox of antiretroviral therapy-induced autoimmunity: the intersecting roles of the Th17/Treg Axis, HLA susceptibility, and accelerated telomeric senescence.","authors":"Hassan H Dib","doi":"10.1080/08830185.2026.2736207","DOIUrl":"https://doi.org/10.1080/08830185.2026.2736207","url":null,"abstract":"<p><p>Antiretroviral therapy (ART) has shifted HIV-1 infection into a manageable chronic condition. However, immune reconstitution is occasionally complicated by the de novo emergence of autoimmune diseases (AiDs), presenting a profound immunological paradox. This review evaluates the molecular, phase-specific pathogenetic sequence driving ART-induced autoimmunity at the intersection of cytokine networks, host genetics, and nuclear senescence. A systematic literature search (1985-2026) was conducted across PubMed, Embase, and Scopus using high-density Boolean strings targeting HIV, AiDs, immune reconstitution inflammatory syndrome, cytokines, and telomeric metrics. Results indicate that immune repopulation occurs in distinct phases matching memory and naive T-cell waves. Host immunogenetics heavily regulate susceptibility; mathematical derivation yields a Relative Risk (RR) ratio of 1.12 for individuals lacking the protective HLA-DRB1*13 allele. Chronic retroviral stress and high reactive oxygen species accelerate telomeric erosion. Critically shortened telomeres are associated with a DNA damage response, which may promote an immune cell transition into a Senescence-Associated Secretory Phenotype (SASP) marked by elevated Interleukin-6 (IL-6) secretion. Elevated IL-6 signaling is linked to altered peripheral tolerance, potentially shifting the Th17/Treg axis toward pathogenic Th17 cell differentiation. Post-ART autoimmunity is associated with accelerated immunosenescence, Th17/Treg imbalances, and hypothesized post-transcriptional controls governed by the Arid5a/Regnase-1 balance over IL-6 transcripts.</p>","PeriodicalId":14333,"journal":{"name":"International Reviews of Immunology","volume":" ","pages":"1-14"},"PeriodicalIF":5.4,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149109611","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":"NF-κB signaling in persistent high-risk cervical HPV infection: Clinical evidence, molecular mechanisms, and translational therapeutic opportunities.","authors":"Maryam Mashhadi Abolghasem Shirazi","doi":"10.1080/08830185.2026.2736241","DOIUrl":"https://doi.org/10.1080/08830185.2026.2736241","url":null,"abstract":"<p><p>Persistent infection with high-risk human papillomavirus (HPV) is the essential precursor to cervical carcinogenesis and remains a major global health challenge despite advances in vaccination and screening. While most cervical HPV infections are spontaneously cleared, a subset persists and progresses to cervical intraepithelial neoplasia (CIN) and ultimately invasive cervical cancer. Emerging evidence identifies nuclear factor kappa B (NF-κB) as a central regulator linking antiviral immunity, chronic inflammation, epithelial survival, and disease progression. In this hybrid review, we systematically synthesize clinical evidence regarding NF-κB activation in persistent cervical high-risk HPV infection and integrate mechanistic insights from molecular studies to develop a translational framework for therapeutic intervention. Current data suggest that HPV oncoproteins E6 and E7 selectively reprogram NF-κB signaling, attenuating antiviral interferon responses while maintaining inflammatory pathways that favor viral persistence and immune dysregulation. A stage-dependent model emerges in which early suppression of antiviral signaling is followed by chronic low-grade NF-κB activation, promoting epithelial survival, microenvironmental remodeling, and progression toward high-grade CIN. We further discuss pathway-specific therapeutic opportunities, including selective NF-κB modulation and integration with therapeutic E6/E7 vaccination. Collectively, NF-κB represents a promising biomarker and therapeutic target for host-directed strategies aimed at viral clearance and prevention of cervical cancer progression.</p>","PeriodicalId":14333,"journal":{"name":"International Reviews of Immunology","volume":" ","pages":"1-19"},"PeriodicalIF":5.4,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149074614","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":"Extracellular vesicle signaling in regulatory T cell biology: From immune suppression to microenvironmental crosstalk.","authors":"Shruti Talekar, Vibha Lade, Sayantani Ghosh","doi":"10.1080/08830185.2026.2736246","DOIUrl":"https://doi.org/10.1080/08830185.2026.2736246","url":null,"abstract":"<p><p>Regulatory T cells (Tregs) are essential for maintaining immune homeostasis, yet classical suppressive mechanisms alone do not fully explain how tolerance is propagated across tissues and sustained over time. Extracellular vesicles (EVs), particularly exosome-enriched small EVs, have emerged as an important additional layer of Treg-associated communication by enabling the selective transfer of proteins, lipids and regulatory RNAs between cells. In this review, we examine the reciprocal EV-Treg axis, highlighting how Treg-derived EVs extend suppressive function beyond direct cell contact by modulating dendritic cells, restraining effector T-cell responses, promoting regulatory macrophage polarization and supporting tissue repair. We further discuss how EVs released by immune, epithelial, stromal, microbial and tumor-associated cells shape Treg differentiation, stability and functional specialization in diverse physiological and pathological settings. Across autoimmunity, transplantation, barrier inflammation, infection and cancer, this bidirectional crosstalk emerges as a context-dependent regulator of immune tolerance that may either preserve tissue homeostasis or promote pathological immune suppression. We finally consider the therapeutic potential of targeting or engineering EV-Treg interactions as a cell-free strategy for precision immunomodulation.</p>","PeriodicalId":14333,"journal":{"name":"International Reviews of Immunology","volume":" ","pages":"1-22"},"PeriodicalIF":5.4,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149074620","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":"Regulatory T cells as drivers of CNS remyelination: neuro-immune cross-talk and comparative insights from mammalian and zebrafish models.","authors":"Debasmita Baidya, Tandra Sarkar, Biman Kanti Ray, Subhra Prakash Hui","doi":"10.1080/08830185.2026.2725546","DOIUrl":"https://doi.org/10.1080/08830185.2026.2725546","url":null,"abstract":"<p><p>Demyelination of the Central Nervous System (CNS) is a pathological process that causes the destruction of the myelin sheath, the insulating cover that protects the nerve fibres. This serves as one of the major attributes of numerous neurological disorders, such as Multiple Sclerosis (MS), Neuromyelitis Optica Spectrum Disorder (NMOSD), Acute Disseminated Encephalomyelitis (ADEM), Myelin Oligodendrocyte Glycoprotein-related antibody disease (MOGAD), etc. It is usually initiated as an immune-mediated injury to myelin, followed by dysregulation of the immune system and ultimately failure of effective remyelination. Although oligodendrocytes in the CNS have some capacity for regeneration, the surrounding microenvironment severely inhibits their function, which results in a reduced regenerative outcome. Previously referred to as suppressor T cells, regulatory T cells (Tregs) are a subset of T cells that were traditionally thought to have an immunosuppressive function. However, it has just recently been shown that they directly contribute to regeneration and repair. The goal of this review is to demonstrate how Tregs can promote regeneration by balancing a variety of underlying molecular and cellular processes. Recent research shows that Tregs affect oligodendrocyte lineage progression, microglial and astrocytic responses, and the milieu around the demyelination site in order to perform remyelination. These effects are age-dependent and occur both temporally and geographically. In order to offer an evolutionary perspective on the conserved immune-mediated regenerative pathways that may be diminished in mammals and can be further investigated for therapeutic purposes, this review also aims to draw comparisons between the mechanisms used by regeneration-competent and non-competent species.</p>","PeriodicalId":14333,"journal":{"name":"International Reviews of Immunology","volume":" ","pages":"1-16"},"PeriodicalIF":5.4,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148976894","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":"Immunosenescence and immune-organ axis dysfunction: Potential of algal bioactives and nutritional interventions for healthy ageing.","authors":"Ramkumar Thilagavathy, Ravi Pandiselvam, Nagamaniammai Govindarajan","doi":"10.1080/08830185.2026.2729156","DOIUrl":"https://doi.org/10.1080/08830185.2026.2729156","url":null,"abstract":"<p><p>Aging-associated immunosenescence disrupts various immune pathways-signaling, cellular, metabolic, epigenetic, and inflammatory mechanisms-leading to impaired bidirectional interactions between the immune system and organs. This dysfunction exacerbates geriatric conditions, including neurodegenerative disorders, chronic inflammation, and metabolic syndromes. This review introduces the concept of the immune-organ axis, an underexplored framework connecting immune dysregulation to organ-specific dysfunction. Nutritional interventions, including bioactive compounds, essential nutrients, functional foods, and phytochemicals, are highlighted for their ability to modulate these pathways by inducing autophagy, resolving inflammation, and promoting cellular repair. Furthermore, stabilization and delivery systems are proposed as technological solutions to enhance the efficacy of these interventions. This review emphasizes the need for integrative approaches to mitigate immune dysfunction and improve health outcomes in aging populations, while outlining future research directions to advance this field.</p>","PeriodicalId":14333,"journal":{"name":"International Reviews of Immunology","volume":" ","pages":"1-25"},"PeriodicalIF":5.4,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148976851","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":"Regulatory T cells in the tumor microenvironment: Mechanisms and clinical implications.","authors":"Haewon Song, Jihyun Kim, Sung-Min Hwang","doi":"10.1080/08830185.2026.2696076","DOIUrl":"https://doi.org/10.1080/08830185.2026.2696076","url":null,"abstract":"<p><p>Regulatory T cells (Tregs) are essential mediators of immune tolerance that maintain tissue homeostasis by restraining excessive immune activation. In cancer, these regulatory mechanisms are reinforced within malignant tissues and contribute to suppression of endogenous anti-tumor immunity. Tumor-infiltrating Tregs (TI-Tregs) represent a specialized activation state shaped by chronic antigen exposure, inflammatory cytokines, stromal cues, and metabolic stress imposed by the tumor microenvironment (TME). Rather than functioning as a static suppressive lineage, intratumoral Tregs integrate receptor-mediated signaling, FOXP3-centered transcriptional stabilization, and metabolic licensing, and spatial niche formation to maintain suppressive fitness under hypoxic and nutrient-restricted conditions. This review synthesizes current understanding of the molecular and metabolic programs that stabilize tumor-associated Tregs and organizes them into an integrated framework linking antigen-driven activation, regulatory identity, metabolic adaptation, tissue-contextual reprogramming, and therapeutic resistance. We further discuss emerging therapeutic strategies aimed at selectively modulating tumor-associated regulatory states while preserving systemic immune tolerance, with explicit attention to preclinical versus clinical evidence, tumor-type specificity, and toxicity risks.</p>","PeriodicalId":14333,"journal":{"name":"International Reviews of Immunology","volume":" ","pages":"1-25"},"PeriodicalIF":5.4,"publicationDate":"2026-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148396792","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":"Metabolic alterations in the tumor microenvironment influence the anti-tumor immune function of CD8⁺ T cells via epigenetic modifications.","authors":"Yaru Liu, Wei Du, Weimin Deng","doi":"10.1080/08830185.2026.2687543","DOIUrl":"https://doi.org/10.1080/08830185.2026.2687543","url":null,"abstract":"<p><p>Metabolic reprogramming within the tumor microenvironment (TME) is a pivotal driver of CD8⁺ T cell dysfunction in cancer. Tumor cells outcompete T cells for essential nutrients, including glucose and amino acids, while accumulating immunosuppressive metabolites such as lactate and 2-hydroxyglutarate. Beyond direct functional impairment, emerging research reveals that these metabolic alterations orchestrate CD8⁺ T cell transcriptional programs by remodeling their epigenome-<i>via</i> histone modifications, DNA methylation, and non-coding RNA networks-thereby dictating their differentiation, cytotoxic potential, and memory formation. A deeper understanding of how TME-derived metabolic signals shape the epigenetic landscape of CD8⁺ T cells is crucial for improving current cancer immunotherapeutic strategies. This review systematically delineates how key TME metabolic features, including nutrient deprivation and oncometabolite accumulation, regulate CD8⁺ T cell fate through epigenetic pathways. Furthermore, we discuss promising therapeutic strategies that target the metabolism-epigenetics axis to reinvigorate CD8⁺ T cell anti-tumor immunity, offering novel perspectives for enhancing adoptive cell therapy and immune checkpoint blockade.</p>","PeriodicalId":14333,"journal":{"name":"International Reviews of Immunology","volume":" ","pages":"1-18"},"PeriodicalIF":5.4,"publicationDate":"2026-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148338583","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":"Macrophage markers and gene signature profiling reveals mesenchymal stem cells mediated immune modulation in Plasmodium berghei ANKA infection.","authors":"Aarti Gupta, Reva Sharan Thakur, Rajesh Kumar Ojha, Tahseen Khan, Meenu Kalkal, Jyoti Das","doi":"10.1080/08830185.2026.2683964","DOIUrl":"https://doi.org/10.1080/08830185.2026.2683964","url":null,"abstract":"<p><strong>Background: </strong>Cerebral malaria (CM) is a life-threatening neurological complication of <i>Plasmodium falciparum</i> infection characterized by excessive inflammation, blood-brain barrier (BBB) disruption, and immune dysregulation. Macrophage-mediated inflammatory responses play a central role in CM pathogenesis, where imbalanced activation contributes to disease progression and tissue damage. However, integrated analyses combining macrophage surface phenotyping with transcriptional profiling remain limited, restricting comprehensive understanding of immune modulation during CM.</p><p><strong>Objective: </strong>To investigate the prophylactic immunomodulatory effects of MSCs administration in experimental CM and evaluate its impact on splenic macrophage responses.</p><p><strong>Methods: </strong>C57BL/6 mice infected with Pb.ANKA received intravenous MSC administration on the day of infection and were monitored for parasitemia and survival. BBB integrity was assessed using Evans blue extravasation, and brain pathology was evaluated histologically. MSC biodistribution was analyzed using near-infrared labeling. Macrophage polarization in F4/80⁺CD11b⁺ splenic cells was assessed by flow cytometry using M1 markers (CD86, CD38) and M2 markers (CD163, CD206, EGR-2). Gene expression of macrophage-associated markers (iNOS-2, Arginase-1, FPR-1, GPR-18, PTGES-2, EGR-2) was analyzed by quantitative real-time PCR.</p><p><strong>Results: </strong>MSC administration reduced parasitemia, improved survival, preserved BBB integrity, and attenuated brain pathology. MSCs showed systemic distribution, suggesting peripheral immune modulation. Flow cytometry revealed reduced M1 markers with maintained or enhanced M2 markers. Gene expression showed downregulation of iNOS-2 and upregulation of Arginase-1, EGR-2, GPR-18, FPR-1, and PTGES-2, indicating macrophage reprogramming toward a balanced M1/M2 continuum.</p><p><strong>Conclusion: </strong>MSC administration mitigates disease severity in experimental CM by modulating macrophage polarization, promoting a balanced M1/M2 response, attenuating inflammatory pathways, and preserving BBB integrity.</p>","PeriodicalId":14333,"journal":{"name":"International Reviews of Immunology","volume":" ","pages":"1-19"},"PeriodicalIF":2.9,"publicationDate":"2026-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148211352","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":"Understanding the role of regulatory T cell-derived small extracellular vesicles in suppression of anti-tumor immune response: Key to advancing cancer immunotherapy.","authors":"Pranav Seth, Subrata Kumar Pore, Sonja Ludwig, Priyanka Sharma","doi":"10.1080/08830185.2026.2631464","DOIUrl":"10.1080/08830185.2026.2631464","url":null,"abstract":"<p><p>Regulatory T cells (Tregs) represent a distinct T cell subpopulation crucial for preserving immune homeostasis. Their primary function is to facilitate self-tolerance and suppress other immune responses, achieved through multifaceted mechanisms, including the secretion of extracellular vesicles (EVs) such as exosomes, which effectively modulate the activity of other innate and adaptive immune cells. Treg-derived extracellular vesicles (Treg-EVs) are minute, membrane-bound vesicles containing specific biological molecules, comprising proteins, nucleic acids, and lipids. Upon transfer to target cells, these molecules exert diverse effects on immune responses. The Treg-mediated immune suppression process encompasses several contact-dependent and contact-independent mechanisms. These encompass the expression of various inhibitory receptors, such as CTLA-4, PD-1, CD39, and CD73, which serve to regulate the immune response. Furthermore, Tregs exhibit the capacity to directly eliminate target cells through the expression of perforin and granzyme B. Additionally, Tregs produce immunosuppressive cytokines that play a pivotal role in maintaining immune system equilibrium. Studying the impact of Treg-derived exosomes on the immune system in cancer is crucial for advancing cancer research and treatment. Understanding these interactions is vital for unraveling the potential implications for cancer development and progression.</p>","PeriodicalId":14333,"journal":{"name":"International Reviews of Immunology","volume":" ","pages":"161-183"},"PeriodicalIF":5.4,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147432850","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":"CKS2, regulated by METTL3, contributes to osteosarcoma progression in an IGF2BP1-dependent manner.","authors":"Zhiyong Feng, Li Zhang","doi":"10.1080/08830185.2026.2641449","DOIUrl":"10.1080/08830185.2026.2641449","url":null,"abstract":"<p><strong>Background: </strong>Emerging evidence implicates N6-methyladenosine (m⁶A) RNA modification in osteosarcoma (OS) pathogenesis, but the downstream effectors and regulatory networks remain not fully elucidated. Cyclin-dependent kinase subunit 2 (CKS2) has been identified as a potential key player in OS. This study investigates its role in OS progression and its regulation <i>via</i> METTL3-mediated m⁶A modification.</p><p><strong>Methods: </strong>Differentially expressed genes (DEGs) were analyzed using the GSE16088 dataset from the GEO database. Candidate targets were validated in OS tissues by qRT-PCR, and the gene with the highest fold change was selected. The role of CKS2 was examined using <i>in vitro</i> and <i>in vivo</i> assays. The relationships among CKS2, METTL3, and IGF2BP1 were analyzed <i>via</i> bioinformatics, correlation analysis, RIP, MeRIP, qRT-PCR, Western blotting, and mRNA stability assays. Rescue experiments explored the functional relationship between METTL3 and CKS2.</p><p><strong>Results: </strong>CKS2 was identified as one of the most upregulated genes in OS, a finding confirmed in OS tissues. Its silencing suppressed OS cell proliferation, colony formation, migration, invasion, and tumor growth. Furthermore, METTL3 expression was positively associated with CKS2 levels, and METTL3 overexpression increased CKS2 mRNA stability in an m⁶A-dependent manner. Interestingly, IGF2BP1 bound directly to m⁶A-modified CKS2 transcripts and maintained their stability. Functionally, METTL3 overexpression partially rescued the suppressive effects of CKS2 silencing on OS cells.</p><p><strong>Conclusions: </strong>Our study identified a METTL3/IGF2BP1-CKS2 axis that promotes OS progression <i>via</i> m⁶A-dependent mRNA stabilization, highlighting CKS2 as a potential therapeutic target.</p>","PeriodicalId":14333,"journal":{"name":"International Reviews of Immunology","volume":" ","pages":"149-160"},"PeriodicalIF":5.4,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147443600","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}