Immunology最新文献

{"title":"Vaginal Microbiota and Ovarian Cancer: A New Frontier in Immunomodulation and Diagnosis.","authors":"Wafa Babay, Mariem Garci, Ahmed Baligh Laaribi, Nabil Mathlouthi, Imene Ouzari","doi":"10.1111/imm.70112","DOIUrl":"10.1111/imm.70112","url":null,"abstract":"<p><p>Ovarian cancer remains one of the deadliest gynaecological cancers due to its often-late diagnosis and the absence of specific symptoms in the early stages. Beyond genetic alterations, the tumour microenvironment, including the vaginal microbiota, plays a decisive role in tumour progression. Recent studies have highlighted the involvement of microbial imbalance 'dysbiosis' in ovarian carcinogenesis, particularly through interactions with the immune system and the modulation of local inflammatory pathways such as Th17-related pathways. In a state of 'eubiosis,' the vaginal microbiota, dominated by Lactobacillus species, plays a protective role by producing lactic acid, maintaining an acidic pH, and preventing infections. Conversely, dysbiosis, characterised by a decrease in lactobacilli and an increase in opportunistic bacteria such as Gardnerella, Atopobium and Prevotella, promotes chronic inflammation through Toll-like receptor signalling, stimulates the production of IL-6, IL-8 and TNF-α, thereby creating a pro-tumour immune microenvironment conducive to tumour development. The complex interactions of the microbial flora, mucosal immunity, and tumour cells could explain the association between vaginal microbiota and ovarian cancer. This review highlights these mechanisms and emphasises the potential of vaginal microbiota as a tool for early detection and improved diagnosis of ovarian cancer. A better understanding of this microbe-host dialogue could pave the way for new prevention and detection strategies.</p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":" ","pages":"209-217"},"PeriodicalIF":5.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13135882/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146018461","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bacterial Coinfection in Critically Ill Patients With COVID-19.","authors":"Mateusz Bartoszewicz, Edyta Wilczyk-Chrostek, Sławomir Lech Czaban, Jerzy Robert Ładny, Marta Krysik","doi":"10.1111/imm.70107","DOIUrl":"10.1111/imm.70107","url":null,"abstract":"<p><p>Intensive care unit (ICU) patients with coronavirus disease 2019 (COVID-19) have an increased risk of bacterial coinfections, including ventilator-associated pneumonia (VAP), bloodstream infections (BSI) and catheter-associated urinary tract infections (CA-UTI). The objective was to investigate the prevalence, risk factors and spectrum of bacterial coinfections in patients with COVID-19 admitted to the ICU. It is a single-centre retrospective cohort study. Data from 201 patients with COVID-19 admitted to the University Clinical Intensive Care Hospital in Bialystok, Poland, between March 2020 and July 2021 were analysed. The prevalence of coinfections, risk factors and causative agents were assessed. Objective comparisons of data were performed by evaluating related studies and reviews. Bacterial coinfections developed in 70% of the 201 patients studied. The most frequent types were VAP, occurring in 47.5% of patients with bacterial coinfections, BSI and CA-UTI. Prolonged ventilatory support (mean duration of 13.3 days in the bacterial coinfection group) and prolonged ICU stay (mean of 15.3 days) were associated with an increased risk of these infections. The predominant pathogens were Klebsiella pneumoniae and Staphylococcus aureus , with Klebsiella pneumoniae extended spectrum beta-lactamases (ESBL) being the most frequently isolated pathogen after 48 h of ICU admission, detected in 121 instances. Bacterial coinfections are common in COVID-19 patients in the ICU and are associated with specific risk factors and pathogens. Vigilant monitoring, antimicrobial stewardship and infection prevention measures are needed to improve patient outcomes.</p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":" ","pages":"231-248"},"PeriodicalIF":5.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145989149","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Amino Terminal Region of Crimean-Congo Hemorrhagic Fever Virus (CCHFV) Nucleocapsid (NP) Protein Contains Dominant Epitopes Recognised by Cellular Immunity.","authors":"Aysegul Pirincal, Sercan Keskin, Mehmet Ziya Doymaz","doi":"10.1111/imm.70119","DOIUrl":"10.1111/imm.70119","url":null,"abstract":"<p><p>Crimean-Congo hemorrhagic fever virus (CCHFV) is a tick-borne orthonairovirus associated with severe hemorrhagic fever and high mortality in humans. The genome is comprised of three segments of single-stranded, negative-sense RNA. The nucleocapsid (NP) protein, which is the focus of our study, encoded by the smallest (S) segment, plays a central role in viral RNA encapsidation and is known to be highly immunogenic, eliciting innate, humoral and cellular immune responses. This study aimed to identify the immunodominant regions of the NP that trigger T cell-mediated immune responses. To this end, three truncated variants of the NP from the CCHFV Kelkit'06 strain [NPdelN(1-135 aa), NPdelM(136-295 aa) and NPdelC(296-482 aa)] as well as the full-length NP(1-482 aa) were tested. Following mice immunisations, local lymph node cells were used as the source of lymphocytes and these cells were assessed to gauge the T cell responses. Stimulated splenocytes were analysed for lymphoproliferative responses and cytokine mRNA expression to evaluate T cell polarisation. Based on the data obtained, it appears that the amino-terminal region (1-135 amino acids) of NP is significantly more immunogenic than the other regions. In contrast, the carboxy-terminal region (296-482 aa) appears to play a suppressive role in cellular immune activation. Additionally, the middle region (136-295 aa) of the NP is identified as being responsible for inducing Th17-type cellular immune responses. In conclusion, this study points out to the specific regions of the CCHFV NP that are involved in shaping the cellular immune responses, representing a crucial step toward refining the structural elements contributing anti-viral immunity and providing a sound ground for modulation efforts.</p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":" ","pages":"336-347"},"PeriodicalIF":5.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146131849","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PI3Kγ Pathway Contributes to Neuroinflammation and Neuronal Death Induced by Zika Virus Infection.","authors":"Danielle Cunha Teixeira, Gabriel Campolina-Silva, Fernanda Martins Marim, Felipe Rocha da Silva Santos, Celso Martins Queiroz-Junior, Pedro Augusto Carvalho Costa, Fernanda de Lima Tana, Luiz Pedro Souza-Costa, Jordane Clarisse Pimenta, Júlia Gomes Carvalho, Vinícius Amorim Beltrami, Felipe Emanuel Oliveira Rocha, Drielle Viana Vieira, Evandro Gonçalves Dornelas, Giovana Cougo Ferreira, Felipe Ferraz Dias, Pedro Pires Goulart Guimarães, Vinícius Toledo Ribas, Fabiola Mara Ribeiro, Antonio Lucio Teixeira, Aline Silva de Miranda, Mauro Martins Teixeira, Daniele da Glória Souza, Vivian Vasconcelos Costa","doi":"10.1111/imm.70113","DOIUrl":"10.1111/imm.70113","url":null,"abstract":"<p><p>Zika virus (ZIKV) is an emerging arbovirus belonging to the Flaviviridae family and Orthoflavivirus genus, with a pronounced tropism for the central nervous system (CNS), where it induces neuroinflammation and neuronal death. ZIKV is known to exploit host cellular mechanisms, including the activation of survival pathways such as the PI3K/AKT signalling cascade, to evade apoptosis and enhance its replication. However, the role of the PI3Kγ isoform in ZIKV-induced neuroinflammation has not been previously explored, and this study aimed to investigate PI3Kγ in ZIKV pathogenesis. Primary neuronal cultures from PI3Kγ-deficient mice (PI3Kγ^kd/kd) and human neuroblastoma SH-SY5Y cells treated with the PI3Kγ inhibitor AS605240 were infected with ZIKV to assess the impact of PI3Kγ signalling on viral replication and neuronal survival. Additionally, interferon α/β receptor knockout (A129) mice were treated with AS605240 either before or after ZIKV infection to evaluate the pathway's role in neuroinflammation. In vitro, both genetic ablation and pharmacological inhibition of PI3Kγ suppressed ZIKV replication (~3% and ~17%, respectively) and prevented neuronal death (~16%). In vivo, mice treated with the PI3Kγ inhibitor exhibited enhanced protection against ZIKV infection, characterised by reduced viral load (~12%) and diminished brain and optic nerve damage. This neuroprotective effect correlated with reduced TNF production (about ~67%) by microglia. Furthermore, inhibition of PI3Kγ curtailed the recruitment and activation of CD8+ T cells and decreased the production of pro-inflammatory mediators, including IFN-γ and IL-17, in the brains of ZIKV-infected mice. These findings suggest that PI3Kγ activation facilitates ZIKV infection and exacerbates neuroinflammation. Pharmacological inhibition of the PI3Kγ pathway may offer therapeutic benefits by limiting viral replication and alleviating neuroinflammatory responses during ZIKV infection.</p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":" ","pages":"318-335"},"PeriodicalIF":5.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146131864","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Benchmarking Dendritic Cell Enrichment Methods Reveals Subset-Specific Recovery Biases.","authors":"Fanny Onodi, Enwono Eyoh, Lucile Massenet-Regad, Margaux Bossis, Diane Biron, Emilie Artru, Vassili Soumelis, Pierre Tonnerre","doi":"10.1111/imm.70145","DOIUrl":"https://doi.org/10.1111/imm.70145","url":null,"abstract":"<p><p>Dendritic cells (DCs) are rare in human blood, often requiring enrichment prior to analysis. Here, we benchmark commonly used pan-DC enrichment methods by comparing recovered DC subset composition to ex vivo references. While all approaches capture major DC populations, recovery is partial and exhibits method-dependent, subset-specific biases. These differences alter the apparent DC composition and may influence downstream analyses. Created with BioRender.com.</p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2026-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147856365","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Stem Cell-Based Delivery of Immunomodulators for Overcoming Glioblastoma Immune Evasion.","authors":"Mustafa T-Ardah, H Malathi, Laxmidhar Maharana, Archana Dhyani, Shaker Al-Hasnaawei, Ashish Singh-Chauhan, Vimal Arora, Jatin Sharma, Manoj Kumar-Mishra","doi":"10.1111/imm.70102","DOIUrl":"10.1111/imm.70102","url":null,"abstract":"<p><p>Glioblastoma (GBM) is the most aggressive primary brain tumour in adults, characterised by rapid progression, extensive heterogeneity, and poor outcomes despite surgery, radiotherapy, and temozolomide (TMZ). A subpopulation of glioblastoma stem cells (GSCs) with self-renewal and multi-lineage differentiation capabilities drives tumour initiation, progression, recurrence, and therapeutic resistance. GSCs evade conventional treatments via enhanced DNA repair, multidrug efflux, activation of survival pathways, epigenetic reprogramming, and entry into quiescent states. Moreover, these cells utilise key immune escape mechanisms, such as downregulation of major histocompatibility complex molecules and the secretion of immunosuppressive factors, to escape detection and destruction by the immune system. Evidence suggests that transformed neural stem cells are a likely source of GSCs, with key survival networks including EGFR, FGFR, HGFR, and PI3K/AKT/mTOR signalling. Their phenotypic plasticity and adaptability to the tumour microenvironment further complicate eradication. Stem cell-based strategies utilising NSCs, MSCs, haematopoietic stem/progenitor cells, or induced pluripotent stem cells can effectively deliver immunomodulators to counteract these immune evasion mechanisms, exploiting tumour tropic migration to deliver therapeutic payloads into hypoxic and infiltrative niches. Approaches such as suicide gene therapy, oncolytic virus delivery, and CXCL12-CXCR4 axis modulation aim to target both proliferative and dormant GSCs. Preclinical studies demonstrate promising efficacy, yet challenges remain, including safety concerns, variability in outcomes, and the limited translational relevance of current models. This review provides a concise overview of GSC biology, resistance mechanisms, and emerging stem cell-based interventions, highlighting opportunities and obstacles in developing effective therapies for GBM.</p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":" ","pages":"23-37"},"PeriodicalIF":5.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145966086","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alterations in NK Cell Function and Glucose Metabolism Characteristics in Patients With Progressive Hepatocellular Carcinoma.","authors":"Lihua Yu, Yuyong Jiang, Xiaoli Liu, Fengna Yan, Huiwen Yan, Yuqing Xie, Wanxin Shi, Zimeng Shang, Juan Du, Zhiyun Yang","doi":"10.1111/imm.70095","DOIUrl":"10.1111/imm.70095","url":null,"abstract":"<p><p>Natural killer (NK) cell immunosuppression represents a critical factor in patients with progressive hepatocellular carcinoma (HCC), yet its underlying characteristics at the single-cell level remain poorly defined. This study investigates the functional and metabolic alterations in NK cells associated with progressive HCC. We performed single-cell RNA sequencing (scRNA-seq) on peripheral blood samples from six treatment-naïve HCC patients, categorised into progressive and stable disease groups based on a 3-year follow-up. This was complemented by multicolor flow cytometry of peripheral blood, alongside multicolor fluorescence analyses of paired tumour and adjacent tissues. Our analyses revealed a significant reduction in NK cell proportion and a marked downregulation of immune-related genes in patients with progressive HCC. scRNA-seq further identified a distinct NK cell characterised by high expression of HAVCR2 (TIM3). Compared to TIM3^-NK cells, TIM3⁺NK cells exhibited an exhausted phenotype, evidenced by upregulated CD39 and TIGIT, impaired functional capacity (reduced CD107a and IFN-γ) and downregulated key glycolytic enzymes (HK2, ATP5a). Clinically, high TIM3 expression correlated with shorter progression-free survival and an increased risk of tumour progression. Collectively, our findings delineate a state of NK cell immunosuppression and metabolic impairment in progressive HCC, potentially driven by glycolytic reprogramming and establish TIM3 as a critical marker and potential therapeutic target.</p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":" ","pages":"186-196"},"PeriodicalIF":5.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145917541","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Role of NLRP1, AIM2 and MEFV Inflammasomes in the High-Intensity Interval Training of Individuals With Obesity.","authors":"Ana Luíza Pereira Assunção Silveira, Daniela Alves de Abreu, Amanda de Lima Santos Musto, Luiz Henrique da Silva Nali, Jônatas Bussador do Amaral, André Luis Lacerda Bachi, Marina Tiemi Shio, Paula Rezende-Teixeira, Carolina Nunes França","doi":"10.1111/imm.70090","DOIUrl":"10.1111/imm.70090","url":null,"abstract":"<p><p>Obesity is a chronic disease associated with systemic inflammation caused by excess visceral fat and pro-inflammatory cytokines such as IL-1β and IL-6. Inflammasomes-particularly those involving genes such as NLRP1, AIM2 and MEFV-play a key role in this process. High-intensity interval training (HIIT) can counteract this inflammation; however, it remains unclear how HIIT modulates inflammasome gene expression in obesity. This study investigated whether HIIT can alter the expression of genes related to the inflammasomes NLRP1, AIM2 and MEFV in obese individuals. The results showed that, after 8 weeks of HIIT, there was an increase in the expression of the genes AIM2, MEFV, CARD16 and CARD18. The increase in CARD16, known to inhibit caspase-1 dimerisation, reinforces the hypothesis related to decreased inflammation, evidenced by the absence of clear activation of the NLRP1 inflammasome and by lower serum IL-1β concentrations in trained participants. Although CARD18 was also upregulated, its function remains ambiguous, and it may act as an inhibitor or modulator of inflammation. Therefore, we conclude that HIIT is a promising intervention for modulating inflammatory genes in individuals with obesity, with the potential to reduce systemic inflammation and its pathological effects.</p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":" ","pages":"109-117"},"PeriodicalIF":5.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13079245/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145804317","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Elevated Peripheral IL-17A-Enriched CD161 ⁺ CCR6 ⁺ CD4 ⁺ T Cells and Their Diagnostic Value in Systemic Lupus Erythematosus.","authors":"Zhonghui Zhang, Xiaochen Sun, Ziqi Xiong, Yiming Gao, Ayibaota Bahabayi, Chen Liu","doi":"10.1111/imm.70100","DOIUrl":"10.1111/imm.70100","url":null,"abstract":"<p><p>Systemic lupus erythematosus (SLE) is an autoimmune disease marked by dysregulated T cell responses and elevated pro-inflammatory cytokines such as IL-17A. Identifying reliable biomarkers could improve diagnosis and understanding of SLE pathogenesis. This study aimed to characterise CD161 and CCR6 expression on peripheral T cells in SLE and evaluate their diagnostic potential. Peripheral blood mononuclear cells were obtained from 34 new onset SLE patients, 26 primary Sjögren's syndrome (pSS) patients and 20 age- and sex-matched healthy controls. Flow cytometry profiled CD4⁺ and CD8⁺ T cells for CD161, CCR6, CXCR3 and intracellular IL-17A. Standard laboratory assays measured complete blood counts, CRP, ESR, complement, immunoglobulins and autoantibodies. Statistical analyses included Student's t-test, Mann-Whitney test, or ANOVA for group comparisons, Spearman's correlation and receiver operating characteristic (ROC) curve analysis with cut-offs determined by the Youden index. A distinct CD4⁺CD161⁺CCR6⁺ subset was present in healthy blood and showed significantly higher IL-17A than CD161⁺CCR6^- or CD161^-CCR6⁺ cells. In SLE patients, the frequency of CD4⁺CD161⁺CCR6⁺ cells was markedly increased compared to healthy controls (median 18.0% vs. 9.2%, p < 0.001) and CD4⁺CD161⁺ alone was also elevated (p < 0.05). ROC analysis distinguishing SLE from healthy controls yielded AUCs of 0.993 for CD4⁺CD161⁺, 0.774 for CD4⁺CD161⁺CCR6⁺ and 0.526 for CD4⁺CCR6⁺. Using pSS as disease controls, CD4⁺CD161⁺CCR6⁺ cells achieved an AUC of 0.868. CD161⁺CCR6⁺ CD4⁺ T cells are enriched for IL-17A and significantly elevated in early SLE, demonstrating moderate diagnostic accuracy. These findings support their potential role as novel blood biomarkers for SLE.</p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":" ","pages":"151-161"},"PeriodicalIF":5.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145863175","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interferon-β Triggers Z-DNA Binding Protein 1-Mediated PANoptosis in T Cells of Anti-Melanoma Differentiation-Associated Protein 5 Antibody-Positive Dermatomyositis.","authors":"Xinxin Zhang, Shiyu Wu, Chao Sun, Yingfang Zhang, Chen Zong, Longyang Zhu, Yiran Chen, Shanshan Li, Qi Pan, Xiaoming Shu, Xin Lu, Guochun Wang, Qinglin Peng","doi":"10.1111/imm.70101","DOIUrl":"10.1111/imm.70101","url":null,"abstract":"<p><p>To investigate the role of PANoptosis activation in anti-melanoma differentiation-associated protein 5 (MDA5) antibody-positive dermatomyositis (anti-MDA5+ DM). Transcriptomic profiling of peripheral blood mononuclear cells (PBMCs) from 40 patients with anti-MDA5+ DM and 10 healthy controls (HCs) was performed. The PANoptosis signature score was constructed using single sample gene set enrichment analysis based on the mean enrichment scores of the pyroptosis, apoptosis and necroptosis gene sets, and the clinical associations of the PANoptosis signature score in patients with anti-MDA5+ DM were evaluated. PANoptosis markers were analysed via western blotting, and the regulatory mechanism of PANoptosis activation was studied in Jurkat cells in vitro. Transcriptomic profiling demonstrated overactivation of the PANoptosis signalling pathway in patients with anti-MDA5+ DM. The PANoptosis signature score was positively correlated with inflammatory markers, type 1 interferon (IFN) signature score, disease severity and poor prognosis in patients with anti-MDA5+ DM. Z-DNA binding protein 1 (ZBP1) was identified as a key PANoptosis-related gene in anti-MDA5+ DM. PANoptosis markers, including P-MLKL, GSDMD-N, cleaved caspase-8, cleaved caspase-3 and cleaved caspase-7, were significantly upregulated in T cells from patients with anti-MDA5+ DM. Functional assays demonstrated that IFN-β induced PANoptosis activation in T cells in vitro, which was significantly attenuated following ZBP1 knockdown. PANoptosis overactivation was associated with disease severity and prognosis in anti-MDA5+ DM. Our findings indicated that IFN-β triggered ZBP1-mediated PANoptosis in T cells, highlighting PANoptosis as a novel potential therapeutic target for anti-MDA5+ DM.</p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":" ","pages":"174-185"},"PeriodicalIF":5.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145911376","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}