Immunology letters最新文献

{"title":"Inhibition of FOSL1 alleviates inflammatory injury of otitis media by reducing ferroptosis.","authors":"Zhuohui Liu, Fan Zhang, Fengfeng Jia, Yongmei Yu, Ruiqing Long","doi":"10.1016/j.imlet.2025.107032","DOIUrl":"https://doi.org/10.1016/j.imlet.2025.107032","url":null,"abstract":"<p><strong>Objectives: </strong>Otitis media (OM) is a disease involving inflammation and infection of the middle ear that primarily affects children. Fos-like antigen 1 (FOSL1), a component of AP1 transcription factor complexes, is a key regulator in inflammation and various diseases. However, the role of FOSL1 in OM remains largely unknown. Our study aimed to elucidate the function and mechanism of FOSL1 in OM.</p><p><strong>Methods: </strong>The gene expression dataset was obtained from Gene Expression Omnibus (GEO), and the differentially expressed genes (DEGs) from OM mice and control mice were identified. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were used to identify potential biological pathways. Gene set variation analysis (GSVA) and gene set enrichment analysis (GSEA) were performed to excavate the biological signaling pathways. The OM cell model was induced by Staphylococcus aureus and Bacillus cereus administration. The expression of FOSL1 and ferroptosis-related proteins in OM cell model were determined by western blot. Inflammatory cytokines in cells were detected by qPCR.</p><p><strong>Results: </strong>DEGs was identified from gene set enrichment (GSE) 49128, 441 genes were up-regulated and 180 were down-regulated. FOSL1 was highly expressed in OM mice. Consistent with the bioinformatic analysis, the expression of FOSL1 in bacterial-induced OM cells was upregulated. Inhibition of FOSL1 via siRNA alleviated the inflammatory response and cell ferroptosis in the OM cell model. The reduced level of inflammatory cytokines and cell ferroptosis induced by FOSL1 inhibition could be rescued by ferroptosis activator erastin.</p><p><strong>Conclusion: </strong>FOSL1 inhibition could alleviate release of inflammatory cytokines and ferroptosis in the OM cell model.</p>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":" ","pages":"107032"},"PeriodicalIF":3.3,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144086187","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":"Low IL-35 Expression in CSF is Associated with Neuro-Behcet Disease: Comparative Analysis Between Parenchymal and Non-Parenchymal NBD.","authors":"Kamel Hamzaoui, Fayçal Haj Sassi, Mariem Salhi, Agnès Hamzaoui","doi":"10.1016/j.imlet.2025.107031","DOIUrl":"https://doi.org/10.1016/j.imlet.2025.107031","url":null,"abstract":"<p><strong>Background: </strong>IL-35 is a recently discovered immunoregulatory cytokine that inhibits inflammatory cytokines by suppressing their lineage-specific transcription factors. The objective of this study was to investigate the expression of IL-35 in the cerebrospinal fluid (CSF) of patients with Neuro-Behçet Disease (NBD). An immuno-comparative analysis was performed between parenchymal NBD (pNBD) and non-parenchymal NBD (npNBD).</p><p><strong>Methods: </strong>We are investigating CSF IL-35 levels in 45 patients with (NBD), comprising 25 patients with pNBD and 20 with npNBD, compared to 27 patients with multiple sclerosis (MS) and 20 patients with non-inflammatory neurological diseases (NIND). We assessed the inflammatory cytokines (IL-1α, IL-18, IL-33, IL-36), Foxp3 and CD4⁺ CD25⁺ Foxp3⁺ regulatory Treg T cells (Tregs). The following methodologies were employed: flow cytometry, ELISA, and real-time polymerase chain reaction (RT-PCR). For RT-PCR analysis, we calculated relative gene expression in target genes using the comparative CT method with the equation 2^-ΔΔCt. We employed a receiver operating characteristic (ROC) curve to investigate the predictive value of IL-35 levels.</p><p><strong>Results: </strong>Protein and relative mRNA expression of IL-35 were significantly decreased in NBD and MS patients compared to the NIND group. Significantly lower CSF IL-35 mRNA (p = 0.0001) and protein (p = 0.0004) were observed in patients with pNBD compared to npNBD. The study revealed that NBD patients exhibited low Treg counts, and a significant positive correlation was identified between Treg numbers and CSF IL-35 (r = 0.554, p = 0.0001). Negative associations were observed between Tregs and CRP (r =- 0.518; p = 0.0001) and ESR (r = -0.571; p = 0.0001) in NBD. Levels of the pro-inflammatory mediators were found to be elevated in contrast to a low Foxp3 level in NBD, which was more reduced in pNBD compared to npNBD. In vitro cultured memory T cells from pNBD patients stimulated with LPS showed high levels of IL-1α, IL-18, IL-33, IL-36 and low levels of Foxp3 and IL-35 measured in the culture medium. After the addition of recombinant human IL-35 (rhIL-35), Foxp3 and IL-35 were significantly increased and inflammatory cytokine levels were reduced. These results suggest that rhIL-35 may induce a regulatory effect on Foxp3 and IL-35.</p><p><strong>Conclusion: </strong>These findings imply a critical reduction of IL-35 in pNBD patients. The combined protein and gene expression of the tested inflammatory cytokines suggest that there are distinct inflammatory mechanisms governing the central nervous system in pNBD. Further work is essential for the development of targeted interventions for the effective treatment of patients.</p>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":" ","pages":"107031"},"PeriodicalIF":3.3,"publicationDate":"2025-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144006647","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":"Quercetin improves macrophage immune regulatory functions to alleviate airway Th2 polarization","authors":"Yixuan Dong ,&nbsp;Le Liu ,&nbsp;Xiwen Zhang ,&nbsp;Haoyue Zheng ,&nbsp;Yu Liu ,&nbsp;Aizhi Zhang ,&nbsp;Lingzhi Xu ,&nbsp;Yuanyi Zhang ,&nbsp;Gui Yang ,&nbsp;Pingchang Yang","doi":"10.1016/j.imlet.2025.107030","DOIUrl":"10.1016/j.imlet.2025.107030","url":null,"abstract":"<div><h3>Background</h3><div>Th2 polarization is a central driver of allergic airway inflammation, yet the epigenetic mechanisms underlying its dysregulation remain poorly defined. Quercetin is a bioactive flavonoid with immunomodulatory properties. This study investigates whether quercetin alleviates Th2-driven pathology in allergic airway inflammation by targeting IL-10 promoter hypermethylation in airway M2 macrophages.</div></div><div><h3>Methods</h3><div>Using a murine model of house dust mite (Derf2)-induced allergic airway inflammation, we isolated airway M2 macrophages via flow cytometry and assessed their immunosuppressive capacity using CFSE-based T cell proliferation assays. Epigenetic regulation of <em>Il10</em> was analyzed by bisulfite sequencing and chromatin immunoprecipitation. Quercetin (intranasal) was administered daily for 7 days.</div></div><div><h3>Results</h3><div>Allergic mice exhibited impaired M2 cell-mediated T cell suppression (proliferation index: 85% vs. 34% in controls, P &lt; 0.01) and IL-10 deficiency in bronchoalveolar lavage fluid (8.5 pg/ml vs. 28.2 pg/ml, P &lt;0.001). Il10 promoter hypermethylation (72% vs. 35% methylation at CpG sites -200 to +100) and reduced KDM5A recruitment were observed in M2 cells from allergic mice. Quercetin treatment reversed these epigenetic defects, restoring KDM5A binding (P &lt; 0.05) and Il10 transcription (2.1-fold increase, P &lt; 0.01), thereby reducing Th2 cytokines and airway hyperresponsiveness.</div></div><div><h3>Conclusions</h3><div>Our findings identify KDM5A-mediated <em>Il10</em> promoter demethylation as a critical mechanism for M2 cell immunoregulation in allergic airway inflammation. Quercetin alleviates Th2-driven pathology by restoring Il10 expression via epigenetic reprogramming of M2 macrophages. This study advances the understanding of natural compounds in targeting epigenetic checkpoints and provides a rationale for quercetin-based therapies in allergic diseases.</div></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":"275 ","pages":"Article 107030"},"PeriodicalIF":3.3,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143899640","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":"Platelet-derived microvesicles modulate cytokine and lipid mediator profiles in THP-1 monocytes and macrophages","authors":"Robert D. Foulem ,&nbsp;Maroua Mbarik ,&nbsp;Jérémie A. Doiron ,&nbsp;Marie-France N. Soucy ,&nbsp;Dayana Toro-Ramirez ,&nbsp;Florient Pecourt ,&nbsp;David A. Barnett ,&nbsp;Luc H. Boudreau ,&nbsp;Marc E. Surette","doi":"10.1016/j.imlet.2025.107029","DOIUrl":"10.1016/j.imlet.2025.107029","url":null,"abstract":"<div><div>Monocytes are circulating immune cells that migrate to inflamed tissues and differentiate into macrophages, where they play a dual role in regulating pro-inflammatory and pro-resolving responses through cytokine and lipid mediator secretion. Platelet-derived microvesicles (PMVs), released during platelet activation, infiltrate inflamed areas and interact with monocytes and macrophages, facilitating the transfer of bioactive contents. While these interactions have been observed, their functional consequences on monocyte/macrophage inflammatory profiles remain poorly understood. In this study, PMVs are shown to be internalized by human THP-1 monocytes. The interaction with THP-1 cells occurs rapidly, with 60 % of cells interacting with PMVs within one hour. When cells are differentiated to M₀ and M₁ macrophages, interactions with PMVs only peak after 24 h. Interaction of cells with PMVs resulted in an increased capacity to synthesize cyclooxygenase- and lipoxygenase-derived lipid mediators of inflammation, especially in M₁ cells. Cytokine production was also influenced in a cell-state-dependent manner. PMVs had no impact on undifferentiated THP-1 cells but enhanced the production of several cytokines in M₀ cells as well as IL-23 and IL-6 in M₁ macrophages. When stimulated with lipopolysaccharides, PMV-treated M₀ macrophages demonstrated elevated production of the anti-inflammatory cytokine IL-10, while M1 macrophages exhibited increased secretion of IL-1β, MCP-1, and IL-6, highlighting an effect on pro-inflammatory cytokine production. These findings reveal that PMVs selectively modulate the inflammatory cytokine and lipid mediator profiles of monocytes and macrophages depending on their differentiation state. This study underscores the role of PMVs as key players in intercellular communication and immune regulation, particularly in the context of inflammation.</div></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":"275 ","pages":"Article 107029"},"PeriodicalIF":3.3,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143924637","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":"Unveiling the hidden syndrome: The enigma of anti-transcobalamin receptor autoantibodies","authors":"Kazuki M. Matsuda,&nbsp;Hirohito Kotani,&nbsp;Shinichi Sato,&nbsp;Ayumi Yoshizaki","doi":"10.1016/j.imlet.2025.107028","DOIUrl":"10.1016/j.imlet.2025.107028","url":null,"abstract":"<div><div>The transcobalamin receptor (CD320) functions as a critical mediator for vitamin B12 uptake in cells, with emerging evidence linking autoantibodies against CD320 to various autoimmune conditions. Pluvinage et al.'s recent study identified anti-CD320 autoantibodies as a cause of autoimmune vitamin B12 central deficiency, specifically affecting the central nervous system while sparing peripheral nerves. Their findings align with our previous work showing anti-CD320′s role in cutaneous arteritis. Both studies identified overlapping CD320 epitopes targeted by autoantibodies and demonstrated the therapeutic efficacy of high-dose vitamin B12 supplementation in mitigating symptoms. Expanding on these findings, we observed anti-CD320 autoantibodies in other inflammatory disorders such as systemic sclerosis, suggesting a broader clinical relevance. The work by Pluvinage et al. and our group supports the concept of an \"anti-CD320-associated syndrome,\" with high-dose B12 supplementation as a promising treatment strategy. Further research is needed to fully elucidate the tissue-specific mechanisms and pathophysiology underlying these autoimmune conditions.</div></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":"275 ","pages":"Article 107028"},"PeriodicalIF":3.3,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143868766","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":"Identification of S100A9 as a target for diagnosis and treatment of Crohn’s Disease after Vedolizumab treatment failure","authors":"Yanru Zhang ,&nbsp;Zhe Zhang ,&nbsp;Ruixian Liu,&nbsp;Yijia He,&nbsp;Shiyang Ning,&nbsp;Junzhi Yu,&nbsp;Yan Liu,&nbsp;Yimeng Xia,&nbsp;Xinji Pang,&nbsp;Wen Lv,&nbsp;Qiankun Sun,&nbsp;Yilong Li,&nbsp;Zhihong Wang,&nbsp;Lu Liu,&nbsp;Baisui Feng","doi":"10.1016/j.imlet.2025.107027","DOIUrl":"10.1016/j.imlet.2025.107027","url":null,"abstract":"<div><div>The vedolizumab medication is the treatment that precisely targets the gut for Crohn’s Disease (CD). It can inhibit the migration of lymphocytes to the intestinal site despite the fact that a significant portion of the population continues to be ineffectively treated. In this study, peripheral blood leukocytes sampled from the CD patients who are nonresponsive or responsive to vedolizumab treatment were used for transcriptome sequencing. Intersected differentially expressed mRNA obtained from transcriptome sequencing and GSE191328 were utilized to predict key therapeutic targets. Bioinformatics analyses were used to explore potential biological mechanisms and to screen pivotal genes. Inhibitor of S100A9 increased the body weight and colon length of mice with colitis, and decreased the DAI score. Our study also demonstrated that the combination of anti-α4β7 integrin antibody with inhibitor of S100A9 further alleviates colitis. Through flow cytometry, changes in the composition of immune cell populations in colon tissues were found after intragastric administration of paquinimod, an inhibitor of S100A9. It is important that blocking S100A9 inhibited the recruitment of neutrophils in the mice’s colon. Our findings lay a foundation for the further exploration of the new targets for non-responders to vedolizumab in CD patients.</div></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":"275 ","pages":"Article 107027"},"PeriodicalIF":3.3,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143941709","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":"NETs activate AIM2 to mediate synovial fibroblast pyroptosis and promote acute gouty arthritis development","authors":"Jing Tian ,&nbsp;Ying Liu ,&nbsp;Wei Gao ,&nbsp;Xiuyun Shi ,&nbsp;Feng Cheng ,&nbsp;Bing Xie","doi":"10.1016/j.imlet.2025.107007","DOIUrl":"10.1016/j.imlet.2025.107007","url":null,"abstract":"<div><h3>Background</h3><div>Acute gouty arthritis is a metabolic disease characterized by hyperuricemia, with acute attacks involving neutrophil-released NETs activating immune responses through their major component, DNA, as danger-associated molecular patterns (DAMPs).</div></div><div><h3>Objective</h3><div>To investigate whether DNA from NETs activates the AIM2 inflammasome in synovial fibroblasts during acute gouty arthritis attacks, inducing pyroptosis and exacerbating inflammation.</div></div><div><h3>Methods</h3><div>The AIM2 gene knockdown mouse model of acute gouty arthritis was constructed, the joint pathological changes were observed by H&amp;E staining, the synovium fibroblasts and neutrophils were sorted by flow cytometry, and the expressions of AIM2, Caspase-1 and GSDMD related proteins were detected by Western blot. The levels of TNF-α, IL-6, IL-1β and IL-18 in serum and cell supernatant were detected by ELISA. Neutrophils were induced to release NETs by urate, and NETs markers (dsDNA, MPO-DNA, NE-DNA) were detected by immunofluorescence (Cit-H3, PAD4) and ELISA. NETs media were co-cultured with synovial fibroblasts, cell activity and migration were evaluated by CCK8 and scrape assay, markers of synovitis (Thy1, VCAM-1, PDPN) were detected by immunofluorescence, and pyroptosis was evaluated by TUNEL and LDH release. By silencing or overexpression of AIM2 gene, Western blot and ELISA, the role of AIM2 in NETs induced pyrodeath and inflammatory response was investigated.</div></div><div><h3>Results</h3><div>AIM2 gene knockdown significantly alleviated the symptoms of MSU-induced acute gouty arthritis in mice, reducing joint swelling and pathological damage. Expression levels of inflammatory factors (TNF-α, IL-6, IL-1β, IL-18) and cleaved Caspase-1/Caspase-1, GSDMD-NT/GSDMD) were decreased. It was found that neutrophils released NETs in response to sodium urate stimulation, manifested by significant upregulation of Cit-H3 and PAD4, as well as increased dsDNA, MPO-DNA, and NE-DNA complexes. NETs can induce inflammatory response in synovial fibroblasts, which is manifested as decreased cell activity and migration ability, increased release of inflammatory factors, and significantly increased markers of synovitis (Thy1, VCAM-1, PDPN). In addition, NETs induce scorch death of synovium fibroblasts by activating AIM2 inflammatories, which aggravates the inflammatory response, and AIM2 gene knockdown can effectively inhibit the scorch death and inflammatory response induced by NETs, indicating that NETs play a key role in the occurrence and development of gout arthritis through AIM2-mediated scorch death of synovium fibroblasts.</div></div><div><h3>Conclusion</h3><div>NETs-activated AIM2-mediated synovial fibroblast pyroptosis plays a crucial role in acute gouty arthritis, providing a new therapeutic target.</div></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":"275 ","pages":"Article 107007"},"PeriodicalIF":3.3,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143855872","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":"Mast cell activation signature as a potential biomarker in COVID-19","authors":"Yatsiri G. Meneses-Preza ,&nbsp;Rodolfo Soria-Castro ,&nbsp;Ángel R. Alfaro-Doblado ,&nbsp;Alejandro Hernández-Solis ,&nbsp;Pablo Álvarez-Maldonado ,&nbsp;Diana Gómez-Martín ,&nbsp;Jiram Torres-Ruiz ,&nbsp;José Francisco Muñoz-Valle ,&nbsp;Guillermina Muñoz-Ríos ,&nbsp;Cristian Oswaldo Hernández-Ramírez ,&nbsp;Azmavet M. Güemes-González ,&nbsp;Isabel Wong-Baeza ,&nbsp;José Luis Maravillas-Montero ,&nbsp;Sonia M. Pérez-Tapia ,&nbsp;Alma D. Chávez-Blanco ,&nbsp;Sergio Estrada-Parra ,&nbsp;Rommel Chacón-Salinas","doi":"10.1016/j.imlet.2025.107026","DOIUrl":"10.1016/j.imlet.2025.107026","url":null,"abstract":"<div><div>The COVID-19 pandemic, caused by the SARS-CoV-2 virus, represented a public health challenge due to the absence of effective treatments to combat the disease. Lethality associated with SARS-CoV-2 infection results from an exacerbated immune response that mediates clinical disease progression and compromises respiratory capacity and organ function. In the lungs, one of the cell lineages increased during COVID-19 are mast cells (MC), cells of innate immune response known for their ability to promote inflammation through the release of their pre-formed mediators or <em>de novo</em> synthesis. The role of MC-derived mediators during SARS-CoV-2 infection and their association with the development of severe COVID-19 have been poorly described. In a previous report, we demonstrated the predictive ability of carboxypeptidase A3 (CPA3) to determine COVID-19 severity. However, it is currently unclear whether the use of other mast cell-derived mediators could improve this predictive ability. To address this gap, we evaluated levels of total tryptase, CPA3, chymase, and prostaglandin D2 (PGD2) in serum from patients with non-severe and severe COVID-19 to develop a predictive model of severe COVID-19 outcomes. We demonstrate that the combined use of these mediators enhances their predictive ability for MC activation during SARS-CoV-2 infection and their involvement in severe forms of COVID-19. Based on these findings, a serum MC activation profile can be proposed as a promising biomarker for SARS-CoV-2 infection and may contribute to the development of targeted therapeutic strategies to improve patient outcomes.</div></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":"275 ","pages":"Article 107026"},"PeriodicalIF":3.3,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143885558","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CD4+ T-cell help delivery to monocyte-derived dendritic cells promotes effector differentiation of helper and cytotoxic T cells","authors":"Douwe M. T. Bosma ,&nbsp;Julia Busselaar ,&nbsp;Mo D. Staal ,&nbsp;Elselien Frijlink ,&nbsp;Matthias Mack ,&nbsp;Fiamma Salerno ,&nbsp;Jannie Borst","doi":"10.1016/j.imlet.2025.107022","DOIUrl":"10.1016/j.imlet.2025.107022","url":null,"abstract":"<div><div>Delivery of CD4⁺ T-cell help optimizes CD8⁺ T-cell effector and memory responses via CD40-mediated licensing of conventional dendritic cells (DCs). Using comparative vaccination settings that prime CD8⁺ T cells in presence or absence of CD4⁺ T-cell help, we observed that CD4⁺ T-cell activation promoted influx of monocytes into the vaccine-draining lymph nodes (dLNs), where they differentiated into monocyte-derived (Mo)DCs, as defined by the most recent standards. Abrogation of these responses by CCR2-targeted depletion indicated that monocyte-derived cells in the dLN promoted T-helper 1 (Th1) type effector differentiation of CD4⁺ T cells, as well as effector differentiation of CD8⁺ T cells. Monocyte-derived cells in dLNs upregulated CD40, CD80 and PD-L1 as a result of CD4⁺ T-cell help. The response of monocyte-derived cells to CD4⁺ T-cell help was independent of natural killer (NK) cells and proceeded via CD40 ligand (L)-CD40 interactions and IFNγ signaling. Our data argue for a scenario wherein activated CD4⁺ T cells in dLNs crosstalk via CD40L and IFNγ signals to monocytes, promoting their local differentiation into MoDCs. This event enhances formation of CD4⁺ Th1 and CD8⁺ cytotoxic effector T cell pool, most likely by virtue of their improved costimulatory status and cytokine production.</div></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":"275 ","pages":"Article 107022"},"PeriodicalIF":3.3,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143877080","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":"A novel MF59 and CpG1018 adjuvant combination enhances the humoral and cellular immune responses against a truncated varicella-zoster viral glycoprotein E","authors":"Jing Yang ,&nbsp;Xue Hu ,&nbsp;Xiguang Chen ,&nbsp;Wanzhen Li ,&nbsp;Quanyi Yin ,&nbsp;Yelin Xiong ,&nbsp;Youcai An ,&nbsp;Haiyan Li ,&nbsp;Zhilei Liu","doi":"10.1016/j.imlet.2025.107025","DOIUrl":"10.1016/j.imlet.2025.107025","url":null,"abstract":"<div><div>Vaccination is the only effective strategy for preventing herpes zoster (HZ), a disease caused by reactivation of the varicella-zoster virus (VZV). Cell-mediated immunity (CMI) plays a pivotal role in controlling VZV reactivation and is a critical factor in the efficacy of the HZ vaccine. This research introduced the preliminary utilization of truncated glycoprotein E (tgE) as the antigen in the formulation of an innovative recombinant HZ vaccine and explored the combination of tgE with several adjuvants to assess their effectiveness in eliciting robust humoral and CMI responses in C57BL/6 mice, followed by the immunogenicity validation of the optimal vaccine formulation in Sprague-Dawley (SD) rats and cynomolgus monkeys. The results demonstrated that the combination of tgE with MF59 and CpG1018, designated as tgE/MF59+CpG1018, elicited significantly stronger gE-specific humoral and cellular immune responses in C57BL/6 mice compared to any single adjuvant or other adjuvant combinations. The optimal dosages for MF59 and CpG1018 were determined to be 0.025 ml and 10 μg, respectively, for each 0.05 ml of the vaccine formulation. Notably, the increasing in the dosage of the adjuvant does not inherently correlate with a more pronounced immune response. Furthermore, the tgE/MF59+CpG1018 also elicited robust humoral and CMI responses in both SD rats and cynomolgus monkeys. These findings established the novel tgE/MF59+CpG1018 vaccine as a highly promising prophylactic candidate against HZ.</div></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":"275 ","pages":"Article 107025"},"PeriodicalIF":3.3,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143839369","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}