Journal of immunology最新文献

{"title":"Generation and characterization of a novel MHC-II tetramer for tracking and characterization of toxin B-specific CD4+ T cell responses.","authors":"Jeffrey R Maslanka, Qianxuan She, Kathleen S Krauss, Emily N Bitsko, Nile U Bayard, Jennifer A Londregan, Mohamad-Gabriel Alameh, Laurence C Eisenlohr, Michele A Kutzler, Joseph P Zackular, Michael C Abt","doi":"10.1093/jimmun/vkag152","DOIUrl":"10.1093/jimmun/vkag152","url":null,"abstract":"<p><p>The gastrointestinal pathogen Clostridioides difficile is a major burden for health systems due to high rates of recurrence. C. difficile pathogenesis is mediated by two virulence factors, toxin A (TcdA) and toxin B (TcdB). Antibodies specific for TcdA and TcdB are correlated with protection from symptomatic recurrence; however, the role for CD4+ T cells is poorly understood in part due to the lack of tools to study the toxin-specific CD4+ T cell response. Our group recently demonstrated the antibody and CD4+ T cell response to C. difficile toxins is impaired via the glucosyltransferase activity of the toxins; however, tools do not exist to study the protective capacity and the phenotype of toxin-specific CD4+ T cells. Therefore, we developed a major histocompatibility complex class II (MHC-II) tetramer to identify TcdB-specific CD4+ T cells via flow cytometry. Herein, we identified an immunodominant epitope (TcdB1961-1975) in the CROPs region of TcdB and optimized an MHC-II tetramer for use in tracking and phenotyping TcdB-specific CD4+ T cell responses following multiple different immunization strategies in mice. Utilizing the tetramer, TcdB-specific T follicular helper cells were detected following TcdB-CROPs messenger RNA lipid nanoparticle vaccination validating the advantage of the tetramer. Furthermore, using a modular messenger RNA vector expressing the TcdB1961 peptide covalently bound to the beta chain of MHC-II, we were able to generate a robust population of TcdB-specific CD4+ T cells. These data outline the generation of new tools for the C. difficile field and lay the groundwork for future studies of toxin-specific CD4+ T cell responses.</p>","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":"215 8","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148759944","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":"CD151 identifies a cytotoxic CD4 T cell population enriched in people with HIV that later develop cancer.","authors":"Mildred Perez, Fangming Zhu, Eric Carlin, Braxton D Greer, Andrew Schroeder, Kelsey E Lowman, Skye Opsteen, Timothy Fram, Christopher Tidwell, Alexandra Duverger, Frederic Wagner, David C Moylan, Lynn Prichard, James Kobie, Sonya L Heath, Paul A Goepfert, Hui Hu, Steffanie Sabbaj, Olaf Kutsch, Nathaniel B Erdmann","doi":"10.1093/jimmun/vkag208","DOIUrl":"10.1093/jimmun/vkag208","url":null,"abstract":"<p><p>People with HIV (PWH) exhibit persistent immune activation despite effective antiretroviral therapy, contributing to risk of non-AIDS-associated comorbidities such as cancer. Cell populations reflecting immune remodeling trajectories preceding malignancy are poorly characterized. Using peripheral blood mononuclear cells from an adult cohort (25-65 yr), we quantified the tetraspanin CD151 on T cells in people without HIV (PWOH), PWH without documented cancer during follow-up, and PWH who subsequently developed a non-AIDS-defining cancer (PWHc), with samples collected a median of 5 yr prior to cancer diagnosis. In PWOH, CD4+CD151+ T cell frequencies increased with age, consistent with physiologic immune aging. In contrast, elevated CD4+CD151+ frequencies were observed at younger ages in both HIV-positive groups, with the typical age-associated increase attenuated. Notably, frequencies were highest in PWHc. CD151 expression was not associated with increased CD25 or CD69, indicating that expansion was not explained by generalized T cell activation. Instead, CD4+CD151+ T cells were enriched for granzyme B and localized predominantly to CD28- effector memory (CD45RA-CCR7-) compartments, consistent with a cytotoxic CD4+ (cCD4) phenotype. Single-cell RNA sequencing of 1 participant per group identified a cCD4+ transcriptional cluster enriched in the PWHc sample. Here, we report that CD151 identifies a cCD4 T cell lineage that accumulates with age in PWOH but appears prematurely expanded in virally suppressed PWH, particularly in PWHc. These findings support CD151+cCD4 T cell expansion as a feature of altered immune remodeling detectable years before cancer diagnosis, suggesting a potential role in mechanisms linking chronic immune dysregulation to malignancy risk in PWH.</p>","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":"215 8","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13433368/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148669757","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":"MiR-221-5p aggravates sepsis-induced myocardial injury by targeting neuropilin-1.","authors":"Yike Zhu, Jinjun Wang, Lingwen Zhang, Xiaozhou Yao, Xingjun Cai","doi":"10.1093/jimmun/vkag228","DOIUrl":"https://doi.org/10.1093/jimmun/vkag228","url":null,"abstract":"<p><p>Sepsis-induced cardiac dysfunction is a primary contributor to mortality, and microRNAs (miRNAs) are recognized as crucial mediators in sepsis pathogenesis. This study aims to identify the key regulatory miRNAs involved in cardiac dysfunction stemming from sepsis. We developed a rat model of sepsis using cecal ligation and puncture (CLP). Myocardial tissue from these rats underwent miRNA sequencing and transcriptome sequencing. Echocardiography was utilized to assess heart function, while cardiac damage was evaluated through HE staining, analysis of inflammatory factors, and detection of tissue injury biomarkers. To model inflammation-induced cardiomyocyte injury, rat cardiomyocyte H9C2 cells were treated with lipopolysaccharide (LPS). Cellular viability was determined using CCK8, and apoptosis was assessed via TUNEL staining and flow cytometry. Oxidative stress levels were analyzed by flow cytometry, and related marker levels were quantified by ELISA. Our results demonstrated that the CLP group displayed substantial cardiac dysfunction, myocardial injury, and elevated inflammatory factor levels. MiR-221-5p was found to be upregulated in both the in vivo and in vitro models. Overexpression of miR-221-5p reduced cardiomyocyte survival while increased apoptotic activity and oxidative stress in LPS-stimulated H9C2 cell. Mechanistically, Neuropilin-1 (NRP1) was identified as a target of miR-221-5p. The cardioprotective effect of miR-221-5p inhibition was reversed by NRP1 knockdown. Furthermore, in vivo administration of a miR-221-5p antagomir mitigated cardiac dysfunction and myocardial damage associated with septic conditions. In conclusion, our findings indicate that miR-221-5p exacerbates septic cardiomyopathy by negatively regulating NRP1, suggesting that the miR-221-5p/NRP1 pathway could represent a novel therapeutic strategy for sepsis-related heart complications.</p>","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":"215 8","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148765049","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":"Innate immune reprogramming of chicken macrophages by sodium butyrate enhances reactive oxygen species-mediated antimicrobial responses in vitro.","authors":"James R Adams, Faisal R Anjum, Muhammad Y Abare, Jai Mehat, Roberto L Ragione, Shahriar Behboudi","doi":"10.1093/jimmun/vkag209","DOIUrl":"https://doi.org/10.1093/jimmun/vkag209","url":null,"abstract":"<p><p>In the established model of classical trained immunity, metabolic and epigenetic hubs serve as central integrators of innate memory. While typically associated with proinflammatory reprogramming, the regulation of autophagy and cellular proteostasis remains essential for guiding macrophage differentiation and ensuring efficient pathogen clearance without excessive inflammation. In this study, we demonstrate that sodium butyrate (SB), a short-chain fatty acid, induces a functional profile that diverges from the canonical pathways observed in classical innate immune training. The induction of an innate reprogrammed state in chicken macrophages by SB is strictly dependent on the cellular developmental stage, occurring only during the early stages of differentiation from chicken bone marrow-derived macrophages but not in fully differentiated cells. This suggests that SB primarily facilitates an innate immune reprogramming with a specific temporal window of sensitivity. Our results show that SB-reprogrammed chicken macrophages exhibit enhanced reactive oxygen species generation, altered cytokine expression, and an increased capacity to kill a diverse range of bacteria. Treatment with chemical inhibitors further demonstrated that these heightened antibacterial effects are directly attributed to increased reactive oxygen species production and autophagy. In summary, these findings indicate that SB induces functional outcomes distinct from classical trained immunity and can elicit innate immune memory through alternative regulatory axes. Our data suggest that distinct innate reprogramming states give rise to alternative activation programs and that innate immune memory exists along a spectrum of phenotypes rather than as a single, uniform state.</p>","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":"215 8","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148712763","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 CXCL10/CXCR3 axis drives actin remodeling to recruit CD4+ T cells to gut epithelium during transmissible gastroenteritis virus infection.","authors":"Chen Tan, Jianing Chen, Yifei Cai, Yang Li, Guohui Wang, Jiangfeng Xie, Guangliang Liu","doi":"10.1093/jimmun/vkag222","DOIUrl":"https://doi.org/10.1093/jimmun/vkag222","url":null,"abstract":"<p><p>The immune system initially protects hosts against viral pathogens, with chemokines guiding immune cell movement. However, their expression patterns and immune cell recruitment mechanisms during transmissible gastroenteritis virus (TGEV) infection are still not fully understood. Here, we identified a distinct chemokine expression profile in intestinal epithelial cells following TGEV infection. Among these, CXCL10 selectively induced the chemotaxis of CD4+ CXCR3+ T cells, while only modestly recruiting CD8+ CXCR3+ (Tc1) T cells and showing minimal involvement in B cell recruitment, thereby shaping the intestinal immune microenvironment to promote TGEV infection. CXCL10 can also upregulate the expression of its receptor CXCR3, thereby further potentiating the migration of CD4+ T cells to the infected region. During this process, CXCL10 activated the CXCR3-Rho GTPase-cofilin signaling axis, driving actin cytoskeletal remodeling. Through this process, CD4+ T cells are channeled from the lamina propria to the infected intestinal lining, facilitating their functional responses. Collectively, these findings reveal a novel mechanism underlying Th1 cell trafficking during TGEV infection and suggest objectives for therapeutic vaccine creation and disease management.</p>","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":"215 8","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148701426","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":"Enforcing mTORC1 activity in therapeutic CD4+ T cells promotes persistence but eventual immune exhaustion.","authors":"Francesca Sillito, Elisa Armbrecht, Aideen T O'Neill, Andrew McIntyre, Melville Nyatondo, Angelika Holler, Lauren A Callender, Sian M Henson, Hans Stauss, Ronjon Chakraverty","doi":"10.1093/jimmun/vkag206","DOIUrl":"https://doi.org/10.1093/jimmun/vkag206","url":null,"abstract":"<p><p>There is substantial interest in developing novel engineering strategies to promote the sustained metabolic fitness of therapeutic T cells. We previously showed that overexpression of RAS homologue enriched in brain (RHEB), a positive regulator of mammalian target of rapamycin complex 1 (mTORC1), promotes aerobic glycolysis and increases the anti-tumor functions of effector CD8+ T cells. To address whether these effects are conserved in CD4+ T cells, we have now examined how enforced activation of mTORC1 activity affects CD4+ T cell differentiation and function. Rheb overexpression induced a more balanced metabolic shift in CD4+ T cells than in CD8+ T cells, with increases in both oxidative phosphorylation and aerobic glycolysis. Although Rheb overexpression initially increased CD4+ T cell activation and proliferation in vitro, the underlying population architecture was complex, involving a shift to both more proliferative, cytotoxic-like cell states as well as more quiescent cell clusters characterised by counter-regulation of mTORC1 activity. Following adoptive transfer, tumor antigen-specific Rheb-transduced CD4+ T cells showed greater persistence but were less efficient than controls in eliminating tumor. This functional deficiency could be explained by a greater propensity of persisting Rheb-transduced CD4+ T cells to develop features of immune exhaustion, as evidenced by expression of multiple co-inhibitory receptors and impaired proliferation upon tumor rechallenge. Together, these data demonstrate the dynamic population response to tuning of T cell mTORC1 and the need to separately appraise cellular outputs of therapeutic CD4+ versus CD8+ T cells when metabolic pathways are manipulated by the same method.</p>","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":"215 8","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148689288","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":"FcγRIII blockade prevents anti-HLA-mediated platelet clearance in a humanized murine model of platelet transfusion refractoriness.","authors":"Lazaro Gil Gonzalez, Kevin Doyoon Won, Zoya Tawhidi, Alequis Pavon Oro, Yaima Tundidor Cabado, Yoelys Cruz-Leal, Akash Gupta, Hanna Wabnitz, Ulrich J Sachs, Rick Kapur, Alan H Lazarus","doi":"10.1093/jimmun/vkag195","DOIUrl":"https://doi.org/10.1093/jimmun/vkag195","url":null,"abstract":"<p><p>Immune platelet transfusion refractoriness (iPTR) is a major complication in transfusion medicine. Although anti-HLA antibodies are recognized contributors, the mechanisms by which they drive platelet clearance remain incompletely defined. We examined sera from 18 patients with iPTR and found that anti-HLA antibodies induced uptake of human platelets expressing the cognate HLA-A2 target antigen and platelet particles derived from these platelets. These sera also mediated clearance of transgenic mouse platelets expressing human HLA-A2. Using THP-1-CD16A macrophages, uptake of both platelets and platelet particles was mediated predominantly through FcγRIIIa, with a partial contribution from FcγRI and little to no role for FcγRII. To test this pathway in vivo, we used a reductionist humanized murine model of iPTR in which HLA-A2 transgenic mouse platelets sensitized with human iPTR sera were transfused into FcγR-humanized mice. In this model, FcγRIII blockade with 17C02-albumin prevented platelet clearance under the conditions tested. These findings extend previous FcγR studies in antibody-mediated platelet clearance to the alloimmune setting of iPTR and support further investigation of FcγRIII-dependent pathways in antibody-mediated PTR.</p>","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":"215 7","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148648742","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":"Kaempferol's potential in targeting IL-17-mediated inflammatory pathways for colorectal cancer treatment.","authors":"Lu Ye, Mengjie Yu, Huilin Liu","doi":"10.1093/jimmun/vkag176","DOIUrl":"https://doi.org/10.1093/jimmun/vkag176","url":null,"abstract":"<p><p>Colorectal cancer (CRC) is a leading malignancy with limited treatment options at advanced stages. Interleukin (IL)-17 signaling promotes tumor progression and immune evasion. Kaempferol, a natural flavonol, has anti-inflammatory and antitumor effects, but its role in modulating IL-17 pathways in CRC is unclear. We used an immunocompetent MC38 xenograft model to evaluate kaempferol monotherapy (50/100 mg/kg), its combination with a PD-L1 inhibitor, and IL-17 overexpression. Tumor growth, immune infiltration, cytokines, and signaling pathways were assessed using immunohistochemistry, enzyme-linked immunosorbent assay, flow cytometry, and Western blotting. Kaempferol suppressed tumor growth in a dose-dependent manner and showed synergistic effects with PD-L1 inhibitors. It enhanced CD4+ and CD8+ T cell infiltration, reduced IL-17A+ γδ T cells, and increased IFN-γ+ γδ T cells. Kaempferol also downregulated IL-6, tumor necrosis factor α, and IL-17A and upregulated IL-2 and interferon γ. Molecular analyses showed inhibition of IL-17A, PD-L1, STAT3, and NF-κB pathway activation. IL-17A overexpression reversed these effects, restoring inflammation, immune suppression, and tumor growth. Kaempferol inhibits CRC progression by targeting IL-17-mediated inflammation and improving antitumor immunity, especially when combined with PD-L1 inhibitors. This study supports kaempferol's potential as a novel therapeutic strategy for CRC.</p>","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":"215 7","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148562069","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":"CD153 promotes B-cell responses to immunization in aged mice.","authors":"Alyssa L Thomas, Joseph A Wayman, Maha Almanan, Autumn Ferguson, Anthony T Bejjani, Emily R Miraldi, Claire A Chougnet, David A Hildeman","doi":"10.1093/jimmun/vkag188","DOIUrl":"10.1093/jimmun/vkag188","url":null,"abstract":"<p><p>We and others have described homeostatic dysregulation of the CD4+ memory T-cell compartment with age. To gain greater insights into this dysregulation, we performed comprehensive single-cell genomic analysis of endogenous memory CD4+ T cells from young and aged mice. This analysis revealed 16 populations, composed of Th1, Th17, several subsets of regulatory T (Treg) cells, memory T cells, CD4+ CTLs, and T follicular helper (Tfh) cells. One of the most highly expressed genes in aged Tfh cells was Tnfsf8 (CD153 or CD30L), and flow cytometric analysis confirmed age-increased expression of CD153 on endogenous Tfh subsets and memory cells, but not Treg cells. At steady state, the absence of IL-6 significantly reduced CD153 expression on Tfh cells, and pharmacologic inhibition of c-MAF prevented IL-6-driven increase in CD153 expression. After immunization, expression of CD153 on Ag-specific CD4+ Tfh cells persisted significantly longer in aged mice, which required IL-6. Blockade of CD153 significantly reduced Tfh cell expression of ICOS and Ag-specific B-cell responses. Thus, although Tfh-mediated B cell responses, overall, normally decline with age, our data suggest that elevated expression of CD153, driven by an IL-6/c-MAF circuit, potentiates remaining Tfh function in aged mice.</p>","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":"215 7","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13385252/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148536134","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":"NAD+ depletion links metabolic stress to drive innate immune priming and selectively control PANoptosis.","authors":"Roman Sarkar, Nagakannan Pandian, Balamurugan Sundaram, Bhesh Raj Sharma, Peter A Gorsuch, Rebecca E Tweedell, Thirumala-Devi Kanneganti","doi":"10.1093/jimmun/vkag203","DOIUrl":"10.1093/jimmun/vkag203","url":null,"abstract":"<p><p>The innate immune system can detect infection, tissue damage, and other homeostatic disruptions to initiate an immune response, drive inflammation, and promote programmed cell death. While these responses can be beneficial in host defense, aberrant activation of inflammatory, lytic cell death pathways can be pathogenic. Emerging evidence suggests that cellular metabolic disruption can promote inflammatory cell death, but the mechanistic connections between these processes are not well understood, limiting our ability to identify regulatory nodes that can be therapeutically targeted. Here, we found that intracellular levels of the metabolic cofactor nicotinamide adenine dinucleotide (NAD+) were depleted in response to cell death triggers that drive pyroptosis, necroptosis, PANoptosis, and ferroptosis. However, restoring NAD+ inhibited PANoptosis but not the other forms of cell death. Mechanistically, NAD+ restoration reduced the expression of PANoptotic sensors or regulators, including the transcription factor IRF1, a critical factor for innate immune sensor priming in PANoptosis. Our findings thereby suggest that NAD+ depletion is an early cell death signaling event and that restoring NAD+ levels specifically blocks PANoptosis by suppressing priming. Hence, targeting NAD+ metabolism represents a potential therapeutic strategy for infectious and inflammatory diseases associated with dysregulated PANoptosis.</p>","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":"215 7","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13403252/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148591935","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}