Molecular immunology最新文献

{"title":"Network pharmacology and in vivo investigation of the growth and immunity-enhancing mechanisms of Tetramethylpyrazine (TMP) in Litopenaeus vannamei","authors":"Renzhi Liu ,&nbsp;Futao Jing ,&nbsp;Zhengxu Chen ,&nbsp;Mingxiang Lu ,&nbsp;Xin Yu ,&nbsp;Yaobing Li ,&nbsp;Luqing Pan","doi":"10.1016/j.molimm.2025.06.009","DOIUrl":"10.1016/j.molimm.2025.06.009","url":null,"abstract":"<div><div>In this study, the shrimp (<em>L. vannamei</em>, 0.89 ± 0.04 g) were fed formulated diets supplemented with Tetramethylpyrazine for six weeks under routine aquaculture conditions, followed by a three-day challenge with White Spot Syndrome Virus (WSSV). The results showed that dietary TMP supplementation significantly improved the specific growth rate and weight gain rate, while reducing the feed conversion ratio. During the viral challenge, the immune protection rate of shrimp was significantly enhanced (<em>P</em> &lt; 0.05). Further analysis using network pharmacology, molecular docking, and quantitative real-time PCR demonstrated that TMP exhibited strong binding affinities with hypoxia-inducible factor 1-alpha (<em>HIF1A</em>), prostaglandin synthase (<em>PTGSH2</em>), and nuclear transcription factors (<em>Relish</em> and <em>Dorsal</em>). At the transcriptional level, TMP significantly inhibited the expression of <em>HIF1A</em> and sterol regulatory element-binding protein (<em>SREBP</em>), while upregulating adiponectin receptor (<em>AdipoR</em>) expression. TMP also promoted lipid catabolismand cholesterol efflux-related genes, while downregulating lipid synthesis genes. Moreover, TMP enhanced the expression of arachidonic acid pathway-related genes and antioxidant enzymes, leading to reduced levels of malondialdehyde (MDA) and blood lipids. Regarding immune stimulation, TMP activated the NF-κB (<em>Dorsal</em>, <em>Relish</em>) signaling pathway, upregulated the expression of antimicrobial peptides, and reduced inflammatory cytokine levels. Under WSSV infection, TMP suppressed viral replication by downregulating <em>HIF1A</em> and <em>VEGF</em> expression (<em>P</em> &lt; 0.05), suggesting that TMP exerts its antiviral effect. High-throughput sequencing of the intestinal microbiota indicated that TMP supplementation increased the abundance of beneficial bacteria and decreased the abundance of harmful bacteria, thereby improving intestinal mucosal barrier function. In conclusion, considering both growth performance and physiological health, we recommend an optimal TMP supplementation level of 150 mg/kg in shrimp feed.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"184 ","pages":"Pages 123-136"},"PeriodicalIF":3.2,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144491270","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 effects of tolerogenic dendritic cells on the TLR4/MyD88/NF-κB signaling pathway in rats with collagen-induced arthritis","authors":"Honghong Li ,&nbsp;Ting Zheng ,&nbsp;Xiufang Wan ,&nbsp;Rui Yuan ,&nbsp;Lunmin Bao ,&nbsp;Tiaoyu Long ,&nbsp;Yan Zhou ,&nbsp;Hongmei Jiang","doi":"10.1016/j.molimm.2025.05.021","DOIUrl":"10.1016/j.molimm.2025.05.021","url":null,"abstract":"<div><h3>Objective</h3><div>Rheumatoid arthritis (RA) is a common inflammatory autoimmune disease. Previous studies have emphasized tolerogenic dendritic cells(tolDCs) could attenuate inflammatory lesions by inducing specific immune tolerance in RA animal models, but the mechanism still needs further investigation. This study focused on revealing the effects of tolDCs on the TLR4/MyD88/NF-κB signaling pathway that mediates inflammation.</div></div><div><h3>Methods</h3><div>Bone marrow-derived tolDCs were induced by IL-4, GM-CSF and NF-κB Oligonucleotide Decoys. The DC-specific molecule OX-62 and co-stimulatory molecules CD80 and CD86 on the surface of tolDCs were detected by flow cytometry. Joint damage was assessed by H&amp;E, Safranine O-fast green staining and tartrate-resistant acid phosphase (TRAP) staining, and the histological change of spleen tissue was also evaluated by H&amp;E staining. Immunohistochemistry (IHC) was performed to detect key proteins of TLR4/MyD88/NF-κB signaling pathway of synovium, cartilage, and bone tissues of ankle joints respectively. Immunofluorescence (IF) was performed to observe NF-κB p65 nuclear translocation and subcellular localization of phosphorylated NF-κB p65 (p-NF-κB p65).</div></div><div><h3>Results</h3><div>The intervention of tolDCs showed a significant reduction in joint inflammation and destruction in CIA rats. Moreover, tolDCs suppressed the hyperactivation of the TLR4/MyD88/NF-κB signaling pathway of the cells in synovium, cartilage and bone tissues of ankle joints in CIA rats.</div></div><div><h3>Conclusions</h3><div>TolDCs may exert therapeutic effects on CIA rats by alleviating the inflammation through inhibiting the hyperactivation of the TLR4/MyD88/NF-κB signaling pathway.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"184 ","pages":"Pages 100-111"},"PeriodicalIF":3.2,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144365352","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":"Cellular interactions in maintaining an inflammatory microenvironment in rheumatoid arthritis","authors":"Subothini Ganeshalingam ,&nbsp;Nicholas J. Wilson ,&nbsp;Sabina Ciciriello ,&nbsp;Juliana Antonipillai ,&nbsp;Adrian A. Achuthan","doi":"10.1016/j.molimm.2025.06.008","DOIUrl":"10.1016/j.molimm.2025.06.008","url":null,"abstract":"<div><div>Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent inflammation and progressive joint destruction, driven by complex pathogenic mechanisms. Aberrant activation of various cellular components and their dynamic interactions contribute significantly to the onset and progression of RA. Key cell types involved include non-immune cells, such as fibroblast-like synoviocytes (FLS) and macrophage-like synoviocytes (MLS), innate immune cells (neutrophils, dendritic cells, and macrophages) and adaptive immune cells (B cells and T cells). These cells collectively release high levels of proinflammatory cytokines (e.g., TNF, IL-1β, IL-6, IL-17, GM-CSF, and lymphotoxins), chemokines (e.g., CCL17, CCL22, CXCL8 and CXCL10), growth factors (e.g., PDGF, and TGF-β), pro-angiogenic factors (e.g., VEGF and FGF), matrix metalloproteinases (e.g., MMP2 and MMP9), and autoantibodies (e.g., RF and ACPA) that collectively contribute to maintaining an inflammatory microenvironment in RA joints. These molecular mediators recruit and activate distinct cellular subsets that perpetuate inflammation. This review provides an overview of the major cellular subpopulations and their intricate interactions within the RA synovium that ultimately lead to sustained synovial inflammation, bone erosion and cartilage damage. In addition, some insights into the potential disruption of such cellular activations and interactions as therapeutic strategies to achieve better treatment outcomes are also provided.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"184 ","pages":"Pages 112-122"},"PeriodicalIF":3.2,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144472121","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":"CD137 might be a pivotal regulator of Th1/Th17-driven autoimmunity and B-cell hyperactivity in hyperthyroidism","authors":"Shuangshuang Li ,&nbsp;Kunyi Li ,&nbsp;Jinying Li ,&nbsp;Yu Wang ,&nbsp;Qiping Shi","doi":"10.1016/j.molimm.2025.06.006","DOIUrl":"10.1016/j.molimm.2025.06.006","url":null,"abstract":"<div><h3>Objective</h3><div>This study aims to investigate the impact of antithyroid drug (ATD) intervention on the expression levels of CD137, IFN-γ, and IL-17 in plasma cytokines, chemokines, and peripheral blood mononuclear cells (PBMCs) of hyperthyroid patients, compared to healthy controls. The goal is to elucidate the involvement of Th cell immune balance, as well as cellular and humoral immunity, in the pathogenesis of hyperthyroidism.</div></div><div><h3>Methods</h3><div>Eighty-one hyperthyroidism patients diagnosed between April 2021 and April 2022 were initially included in the study. Twenty-five patients underwent antithyroid drug (ATD) therapy and were subsequently categorized into the post-intervention group, with an average treatment duration of 129.84 days. Moreover, eighty-three healthy individuals were enlisted as controls. Plasma cytokine concentrations, soluble CD137 (sCD137) levels, and CD137 expression on T and B lymphocytes were evaluated through liquid-phase microarrays, enzyme-linked immunosorbent assay (ELISA), and flow cytometry techniques.</div></div><div><h3>Results</h3><div>1. Compared to the normal control group, the pre-intervention group exhibited elevated peripheral plasma levels of IFN-γ, TNF-α, IL-7, IL-8, IL-17A, MCP-1, MIP-1β, and IL-10. Following ATD intervention, the post-intervention group showed increased peripheral plasma levels of IL-1β, TNF-α, IL-4, and MIP-1β relative to the normal control group. Furthermore, levels of TNF-α, MCP-1, IL-13, and IL-10 were higher in the pre-intervention group than in the post-intervention group (<em>P</em> &lt; 0.05). 2. The percentage of CD19 + B cells in peripheral blood mononuclear cells (PBMCs) was higher in the pre-intervention group than in the normal control group (<em>P</em> &lt; 0.05). 3. The percentages of CD4 +CD137 + T cells, CD8 +CD137 + T cells, and CD19 +CD137 + B cells in PBMCs were greater in the pre-intervention group than in the normal control group (<em>P</em> &lt; 0.05). 4. The concentration of sCD137 in peripheral plasma was higher in the pre-intervention group than in the normal control group (<em>P</em> &lt; 0.05). 5. Levels of IFN-γ and IL-17A secretion by CD4 + T cells, as well as IFN-γ secretion by CD8 + T cells in stimulated PBMCs, were higher in the pre-intervention group than in the normal control group (<em>P</em> &lt; 0.05).</div></div><div><h3>Conclusion</h3><div>Hyperthyroidism is marked by immune dysregulation, evident in altered Th1/Th2/Th17 cytokine expression and elevated CD137 activity. CD137 emerges as a promising biomarker for immune function and a potential therapeutic target.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"184 ","pages":"Pages 89-99"},"PeriodicalIF":3.2,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144313753","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":"Agmatine ameliorates sepsis-related intestinal injury via the AhR-STAT3-IL-10 pathway","authors":"Junhua Pan ,&nbsp;Lianfang Gan ,&nbsp;Yaying Chen ,&nbsp;Lifan Zhong ,&nbsp;Huiming Deng ,&nbsp;Ling Huang ,&nbsp;Huaping Liang","doi":"10.1016/j.molimm.2025.06.004","DOIUrl":"10.1016/j.molimm.2025.06.004","url":null,"abstract":"<div><h3>Background</h3><div>Sepsis-related intestinal injury is essential in multi-organ dysfunction induced by the systemic inflammatory response. Agmatine (AGM) has anti-inflammatory, antioxidative, and immunomodulatory properties. However, no reports of AGM alleviating sepsis-related intestinal injury have been found. Therefore, this study intends to investigate the protective effects of AGM on sepsis-related intestinal injury and its potential mechanism.</div></div><div><h3>Methods</h3><div>We first established a sepsis model by lipopolysaccharide (LPS) or cecum ligation perforation (CLP), and then used H&amp;E staining, transmission electron microscopy (TEM), and TUNEL to examine the pathological changes in rat intestines after AGM treatment. ELISA was used to detect expression levels of inflammatory factors in ileal tissues and biochemical indexes of infectionin in serum. TNF-α induced Caco-2 cell inflammation model was established in vitro, and cell activity and proliferative capacity were detected by CCK8 and EdU after AGM treatment. The Caco-2 cell inflammation model with high or low expression of Aryl hydrocarbon receptor (AhR) was established, and whether AGM exerts anti-inflammatory effects via AhR/STAT3/IL-10 pathway was investigated using molecular docking, Co-IP, and Western Blot.</div></div><div><h3>Results</h3><div>The histopathological staining demonstrated that AGM significantly reduced intestinal injury and the content of inflammatory factors IL-1β, IL-6, and TNF-α, improved systemic infection and the survival rate of septic mice, and restored intestinal barrier function in CLP rats. In vitro, AGM improved cell viability and proliferative capacity of the Caco-2 cell inflammation model. AGM inhibits inflammatory factor expression by activating AhR, decreasing HIF-1 protein expression, and activating the STAT3/IL-10 signaling pathway.</div></div><div><h3>Discussion and conclusion</h3><div>AGM has the potential to ameliorate sepsis-related intestinal injury via the AhR-STAT3-IL-10 pathway, thereby offering theoretical basis for clinical treatment of sepsis.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"184 ","pages":"Pages 76-88"},"PeriodicalIF":3.2,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144270228","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":"Klotho promotes bone formation in rheumatoid arthritis-associated osteoporosis by modulating the Fgf23/Fgfr1/NF-κB pathway and inhibiting ferroptosis","authors":"Lianmei Ji ,&nbsp;Ruina Kong,&nbsp;Yiyi Yu,&nbsp;Wei Wan,&nbsp;Dongbao Zhao,&nbsp;Jie Gao","doi":"10.1016/j.molimm.2025.06.002","DOIUrl":"10.1016/j.molimm.2025.06.002","url":null,"abstract":"<div><h3>Aims</h3><div>Rheumatoid arthritis (RA) frequently leads to osteoporosis (OP) and increased fracture risk. The protein Klotho plays a recognized role in bone metabolism, yet its specific function in RA-associated osteoporosis (RA-OP) remains incompletely understood. This study investigated the molecular mechanisms by which Klotho maintains bone homeostasis in RA-OP patients.</div></div><div><h3>Methods and analysis</h3><div>We quantified Klotho levels in RA-OP patients and healthy controls and then conducted in vitro experiments using mouse embryonic osteoblast precursor cell line (MC3T3-E1) preosteoblastic cells to examine Klotho's effects on osteogenic differentiation and ferroptosis. We assessed osteogenic differentiation through runt-related transcription factor 2 (Runx2), collagen type i alpha 1 chain (Col1a1), and osteocalcin (Ocn) expression, while ferroptosis regulation was evaluated via glutathione peroxidase 4 (Gpx4) and Acyl-CoA synthetase long-chain family member 4 (Acsl4) expression. The interaction between fibroblast growth factor 23 (Fgf23) and fibroblast growth factor receptor 1 (Fgfr1) was analyzed using coimmunoprecipitation assays, with Fgf23's role examined through knockdown and overexpression experiments.</div></div><div><h3>Results</h3><div>Results showed RA-OP patients had significantly reduced Klotho levels compared to controls. Klotho overexpression in MC3T3-E1 cells enhanced osteogenic differentiation and protected against ferroptosis by upregulating Gpx4. Mechanistically, Klotho facilitated Fgf23-Fgfr1 interaction and repressed nuclear factor κ (NF-κB) signaling.</div></div><div><h3>Conclusion</h3><div>Our findings demonstrate that Klotho mediates osteogenic action through the Fgf23/Fgfr1-NF-κB pathway while simultaneously protecting osteoblasts from ferroptosis, advancing our understanding of RA-OP pathophysiology and identifying Klotho as a promising therapeutic target for preventing RA-related bone loss.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"184 ","pages":"Pages 64-75"},"PeriodicalIF":3.2,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144270227","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":"DNA vaccination combined with immune checkpoint inhibition eradicates tumors, inducing life-long immunity against breast cancer in mice","authors":"Allan Noé Domínguez-Romero ,&nbsp;Christian Alejandro Esquivel-García ,&nbsp;Fernando Martínez-Cortés ,&nbsp;Braulio A. Martínez-Zarco ,&nbsp;Josué Odales ,&nbsp;Samir Abraham-Ruiz ,&nbsp;Jorge Maruri ,&nbsp;Vanessa Villegas-Ruiz ,&nbsp;Goar Gevorkian ,&nbsp;Karen Manoutcharian","doi":"10.1016/j.molimm.2025.06.003","DOIUrl":"10.1016/j.molimm.2025.06.003","url":null,"abstract":"<div><div>The employment of cancer vaccines as stand-alone or combined therapies has not yet reached clinically relevant endpoints in large clinical trials in the vast majority of patients, and there is a clear need for novel ideas and qualitatively new vaccine design approaches. In this study, we used a novel Variable Epitope Library (VEL) vaccine strategy, which incorporates thousands to millions of mutated variant epitopes within a combinatorial library, to target extreme variability and intratumoral heterogeneity of tumor antigens. A single intrasplenic vaccination with a VEL DNA vaccine encoding the amino-terminal region of mouse survivin, carrying eight mutated amino acid positions, induced significant tumor growth inhibition and suppression of lung metastasis in an aggressive and highly metastatic 4T1 triple-negative breast cancer (TNBC) preclinical model. Combining this vaccine with an immune checkpoint inhibitor (ICI) αCTLA-4 resulted in the elimination of established tumors, tumor-free survival of up to 412 days and life-long sterile immunity against tumor rechallenge in 77 % of mice. A significant increase in the number of CD3⁺ CD8⁺ Ly6C⁺ effector T cells in the lungs and spleens of vaccinated mice and the presence of central memory (T_CM) and effector memory (T_EM) T cells at different time points was documented. Likewise, the reduction of numbers of CD11b⁺ Ly6C^int Ly6G⁺ granulocytic myeloid-derived suppressor cells (G-MDSC) in vaccinated mice was observed. These data suggest that VEL immunogens are feasible candidates for inclusion/testing in clinical trials targeting multiple cancer types due to their universal nature.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"184 ","pages":"Pages 51-63"},"PeriodicalIF":3.2,"publicationDate":"2025-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144231724","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":"Trogocytosis-mediated acquisition of MHC class II molecules from plasmacytoid dendritic cells confers donor-specific immune tolerance to CD8+CD45RClow/- regulatory T cells","authors":"Yang Zhao ,&nbsp;Lin Zhou ,&nbsp;Zhu-hui Yuan ,&nbsp;Ya-nan Jia ,&nbsp;Qing Chen ,&nbsp;Zhang-yong Ren ,&nbsp;Xin-xue Zhang ,&nbsp;Ren Lang ,&nbsp;Qiang He ,&nbsp;Xian-liang Li","doi":"10.1016/j.molimm.2025.06.001","DOIUrl":"10.1016/j.molimm.2025.06.001","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Objective&lt;/h3&gt;&lt;div&gt;Donor-specific suppression by MHC-II&lt;sup&gt;+&lt;/sup&gt;CD8&lt;sup&gt;+&lt;/sup&gt;CD45RC&lt;sup&gt;low&lt;strong&gt;/-&lt;/strong&gt;&lt;/sup&gt;regulatory T cells (Tregs) was observed in our prior study, here we endeavor to investigate the mechanism underlying generation of the MHC-II&lt;sup&gt;+&lt;/sup&gt;CD8&lt;sup&gt;+&lt;/sup&gt;CD45RC&lt;sup&gt;low&lt;strong&gt;/-&lt;/strong&gt;&lt;/sup&gt;Tregs.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;The presence of MHC-II&lt;sup&gt;+&lt;/sup&gt;CD8&lt;sup&gt;+&lt;/sup&gt;CD45RC&lt;sup&gt;low&lt;strong&gt;/-&lt;/strong&gt;&lt;/sup&gt;Tregs within tolerated grafts was confirmed using a multicolor immunofluorescence technique in spontaneous tolerant rat liver transplant model. We aimed to elucidate the generation mechanism of MHC-II&lt;sup&gt;+&lt;/sup&gt;CD8&lt;sup&gt;+&lt;/sup&gt;CD45RC&lt;sup&gt;low&lt;strong&gt;/-&lt;/strong&gt;&lt;/sup&gt;Tregs by purifying naive CD8&lt;sup&gt;+&lt;/sup&gt;CD45RC&lt;sup&gt;low&lt;strong&gt;/-&lt;/strong&gt;&lt;/sup&gt;Tregs and plasmacytoid dendritic cells (pDCs) from recipients and co-culturing them to induce trogocytosis. Initially, we examined the immunophenotype and cytokine secretion of MHC-II&lt;sup&gt;+&lt;/sup&gt;CD8&lt;sup&gt;+&lt;/sup&gt;CD45RC&lt;sup&gt;low&lt;strong&gt;/-&lt;/strong&gt;&lt;/sup&gt;Treg using flow cytometry. Trogocytosis of peptide-MHC class II complexes was visualized using a confocal microscope. Subsequently, we analyzed the donor-specific inhibitory effect of MHC-II&lt;sup&gt;+&lt;/sup&gt;CD8&lt;sup&gt;+&lt;/sup&gt;CD45RC&lt;sup&gt;low&lt;strong&gt;/-&lt;/strong&gt;&lt;/sup&gt;Tregs using CFSE-based lymphocyte proliferation analysis. Finally, we explored the possible transfer mechanisms of MHC class II using IFN-γ stimulation and 1-MT to block indoleamine-(2,3)-dioxygenase (IDO).&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;In the spontaneously tolerant rat liver transplants, MHC-II&lt;sup&gt;+&lt;/sup&gt;CD8&lt;sup&gt;+&lt;/sup&gt;CD45RC&lt;sup&gt;low&lt;strong&gt;/-&lt;/strong&gt;&lt;/sup&gt;Tregs and IL-10 expression were upregulated. Our in vitro study revealed that trogocytosis occurring between naive CD8&lt;sup&gt;+&lt;/sup&gt;CD45RC&lt;sup&gt;low&lt;strong&gt;/-&lt;/strong&gt;&lt;/sup&gt;Tregs and pDCs could induce MHC-II&lt;sup&gt;+&lt;/sup&gt;CD8&lt;sup&gt;+&lt;/sup&gt;CD45RC&lt;sup&gt;low&lt;strong&gt;/-&lt;/strong&gt;&lt;/sup&gt;Tregs. The semi-direct pathway represents the primary mode of Trogocytosis-mediated transfer of MHC-II molecules from pDCs to CD8&lt;sup&gt;+&lt;/sup&gt;CD45RC&lt;sup&gt;low&lt;strong&gt;/-&lt;/strong&gt;&lt;/sup&gt;Tregs. The MHC-II&lt;sup&gt;+&lt;/sup&gt;CD8&lt;sup&gt;+&lt;/sup&gt;CD45RC&lt;sup&gt;low&lt;strong&gt;/-&lt;/strong&gt;&lt;/sup&gt;Tregs exhibited high secretion of IL-10 and IFN-γ. Co-culturing with MHC-II&lt;sup&gt;+&lt;/sup&gt;CD8&lt;sup&gt;+&lt;/sup&gt;CD45RC&lt;sup&gt;low&lt;strong&gt;/-&lt;/strong&gt;&lt;/sup&gt;Tregs significantly suppressed the proliferation of CD4&lt;sup&gt;+&lt;/sup&gt;CD25&lt;sup&gt;-&lt;/sup&gt;effector T cells. Moreover, this inhibitory effect was donor-specific and could be overcome in the presence of third-party antigen-presenting cells. Our data also suggested that blocking the IFN-γ/IDO signaling pathway could inhibit the generation of trogocytosis-mediated MHC-II&lt;sup&gt;+&lt;/sup&gt;CD8&lt;sup&gt;+&lt;/sup&gt;CD45RC&lt;sup&gt;low&lt;strong&gt;/-&lt;/strong&gt;&lt;/sup&gt;Tregs.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusions&lt;/h3&gt;&lt;div&gt;MHC-II&lt;sup&gt;+&lt;/sup&gt;CD8&lt;sup&gt;+&lt;/sup&gt;CD45RC&lt;sup&gt;low&lt;strong&gt;/-&lt;/strong&gt;&lt;/sup&gt;Tregs generated through trogocytosis exhibit donor-specific suppressive function. Moreover,","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"184 ","pages":"Pages 40-50"},"PeriodicalIF":3.2,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144231723","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":"NSUN3-mediated m5C modification of TAK1 promotes sepsis-induced pulmonary injury through regulating inflammation","authors":"Jingjing Wang,&nbsp;Zhouli Ding,&nbsp;Bo Wu","doi":"10.1016/j.molimm.2025.05.023","DOIUrl":"10.1016/j.molimm.2025.05.023","url":null,"abstract":"<div><h3>Background</h3><div>Sepsis-induced pulmonary injury (SPI) is a life-threatening condition with high mortality. This study aimed to investigate the role of NOP2/Sun RNA methyltransferase 3 (NSUN3) in SPI and its underlying mechanisms.</div></div><div><h3>Methods</h3><div>Bioinformatics analysis of the GSE10474 dataset revealed differentially expressed genes in acute lung injury. A cecum ligation and puncture (CLP) rat model was established. Lung injury was evaluated via hematoxylin and eosin (H&amp;E) staining. Enzyme-linked immunosorbent assay (ELISA) and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) were used to detect inflammatory cytokine mRNA expression and protein levels. In vitro, human lung microvascular endothelial cells (HULEC-5a) were treated with lipopolysaccharide and transfected with NSUN3-silencing or TAK1-overexpression vectors. Methylated RNA immunoprecipitation (MeRIP) and dual-luciferase assays were conducted to investigate the interactions between NSUN3 and transforming growth factor β-activated kinase 1 (TAK1).</div></div><div><h3>Results</h3><div>NSUN3 expression was upregulated in CLP-induced rat lung tissues and LPS-stimulated HULEC-5a cells. NSUN3 inhibition attenuated lung injury and decreased inflammatory cytokine levels in both models. Mechanistically, NSUN3-mediated m⁵C modification enhanced TAK1 mRNA stability in HULEC-5a cells. TAK1 overexpression counteracted the anti-inflammatory effects induced by NSUN3 knockdown.</div></div><div><h3>Conclusion</h3><div>NSUN3-mediated m⁵C modification of TAK1 promoted SPI through regulating inflammation, providing a new insight for SPI treatment.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"184 ","pages":"Pages 32-39"},"PeriodicalIF":3.2,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144221335","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":"Psoralidin induces pyroptosis in both tumor cells and macrophages as well as enhances nature killer cell cytotoxicity to suppress hepatocellular carcinoma","authors":"Xianling Wang ,&nbsp;Yongjian Xie ,&nbsp;Huijie Yang ,&nbsp;Chengxian Li ,&nbsp;Xinru Wen ,&nbsp;Simin Chen ,&nbsp;Qing Yao ,&nbsp;Congyang Zheng ,&nbsp;Chengwei Li ,&nbsp;Caiping He ,&nbsp;Mingxia Fang ,&nbsp;Ce Shi ,&nbsp;Ang Huang ,&nbsp;Ping Zhang ,&nbsp;Zhaofang Bai ,&nbsp;Xiaoyan Zhan ,&nbsp;Xiaohe Xiao","doi":"10.1016/j.molimm.2025.05.020","DOIUrl":"10.1016/j.molimm.2025.05.020","url":null,"abstract":"<div><div>Psoralidin is a major component of the traditional Chinese medicine Psoraleae Fructus, which is derived from the dried mature fruit of the leguminous plant <em>Psoralea corylifolia</em> L. and possesses many pharmacological effects, including anti-tumor effects. However, the mechanism through which psoralidin protects against hepatocellular carcinoma (HCC) remains unclear. In our study, we found that psoralidin induced pyroptosis and gasdermin E (GSDME) cleavage in HepG2 and Hepa1–6 cells, which were reversed by the caspase-3 inhibitor Z-DEVD-FMK. Moreover, psoralidin induced mitochondrial reactive oxygen species (ROS) production, leading to caspase-3 activation and subsequent GSDME cleavage. Interestingly, psoralidin induced pyroptosis in macrophages via ROS-NLRP3 inflammasome-gasdermin D (GSDMD), leading to the secretion of interleukin (IL)-1β and IL-18, which promoted natural killer (NK) cell activation and its anti-tumor capability. In a mouse model, psoralidin suppressed HCC growth, induced tumor cell pyroptosis, and enhanced tumor infiltration of T and NK cells. Collectively, our data demonstrate that psoralidin induces pyroptosis in tumor cells via ROS/caspase-3/GSDME and triggers pyroptosis in macrophages via ROS/NLRP3 inflammasome/GSDMD, enhancing NK cell anti-tumor ability, suggesting that psoralidin could be used as a potential therapeutic candidate for HCC.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"184 ","pages":"Pages 22-31"},"PeriodicalIF":3.2,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144221334","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}