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Electrostatic potential is the dominant force in antigenic selection of naïve T-cells and B-cells for activation and maturation 静电电位是naïve t细胞和b细胞在激活和成熟过程中抗原选择的主导力量。
IF 3.3 4区 医学
Immunology letters Pub Date : 2025-05-23 DOI: 10.1016/j.imlet.2025.107037
Kripa N. Nand, Christopher Bystroff
{"title":"Electrostatic potential is the dominant force in antigenic selection of naïve T-cells and B-cells for activation and maturation","authors":"Kripa N. Nand,&nbsp;Christopher Bystroff","doi":"10.1016/j.imlet.2025.107037","DOIUrl":"10.1016/j.imlet.2025.107037","url":null,"abstract":"<div><div>Peptide antigenicity can be predicted from sequence using a simple method invented by Hopp and Woods in the early 1980′s. Since then, a much clearer understanding of T-cell/B-cell signaling and maturation calls for a new understanding of the amino acid determinants of antigenicity. We show that short peptides with more charged side chains generate significantly higher titers of peptide specific antibodies in co-immunized mice. Peptide docking simulations using linearized Poisson-Boltzmann calculations of electrostatic potential show that immunoglobulins distinguish the cognate peptide sequence from randomly selected sequences at \"arms length\" (10–20 Å) with &gt;70 % of alternative sequences having higher energy at this distance, consistent with the weak specificity observed for naive T-cell and B-cell receptor interactions with MHC-bound antigen. Orders of magnitude lower complexity of the state space of charged surfaces as compared to the state space of surface shapes suggests a dominant role of electrostatics in selecting naive immune cells from the population of circulating cell lines. We propose a two-stage antigen recognition process, first electrostatic and then shape-based, that explains the dominant contribution of charged residues to peptide immunogenicity.</div></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":"276 ","pages":"Article 107037"},"PeriodicalIF":3.3,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144142449","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}
引用次数: 0
Increased expression of membrane-bound TGF-β1, GITR, and GITR ligand in patients with autoimmune thyroid disease 自身免疫性甲状腺疾病患者膜结合TGF-β1、GITR及GITR配体表达升高
IF 3.3 4区 医学
Immunology letters Pub Date : 2025-05-22 DOI: 10.1016/j.imlet.2025.107036
Fumiaki Hayashi , Naoya Inoue , Yoshinori Iwatani , Yuka Yamashita , Hiroya Yamada , Akira Miyauchi , Mikio Watanabe
{"title":"Increased expression of membrane-bound TGF-β1, GITR, and GITR ligand in patients with autoimmune thyroid disease","authors":"Fumiaki Hayashi ,&nbsp;Naoya Inoue ,&nbsp;Yoshinori Iwatani ,&nbsp;Yuka Yamashita ,&nbsp;Hiroya Yamada ,&nbsp;Akira Miyauchi ,&nbsp;Mikio Watanabe","doi":"10.1016/j.imlet.2025.107036","DOIUrl":"10.1016/j.imlet.2025.107036","url":null,"abstract":"<div><div>Regulatory T (Treg) cells, which play an important role in maintaining self-tolerance, are present in the thyroid-infiltrating lymphocytes of patients with autoimmune thyroid disease (AITD). We examined the expression of membrane-bound transforming growth factor-β1 (mTGF-β1), which mediates regulatory function and glucocorticoid-induced tumor necrosis factor receptor-related protein (GITR). The protein in turn may inhibit regulatory function on Treg cells and TGF-β1 receptor II (TGF-βRII) and GITR expression. We also evaluated GITR ligand (GITRL) localization in thyroid tissues. mTGF-β1<sup>+</sup> cells proportion in Treg cells was higher in the thyroid of patients with AITD than in their peripheral blood. GITR<sup>+</sup> cells proportion among Tregs and Teff cells was also higher in the thyroid than in peripheral blood. GITRL expression in thyrocytes was higher in AITD patients than in healthy subjects. The interaction and balance of mTGF-β1, GITR, TGF-βRII, and GITRL especially thyrocyte GITRL expression, could be critical in AITD pathogenesis.</div></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":"276 ","pages":"Article 107036"},"PeriodicalIF":3.3,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144138531","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}
引用次数: 0
The role of DAMP cytotoxic fractions in the immune markers’ disruption in patients with urgent surgical pathology and against the background of post-COVID-19 syndrome 在紧急手术病理患者和covid -19后综合征背景下,DAMP细胞毒性组分在免疫标志物破坏中的作用
IF 3.3 4区 医学
Immunology letters Pub Date : 2025-05-21 DOI: 10.1016/j.imlet.2025.107033
Elena M. Klimova , Olena V. Lavinska , Larisa A. Drozdova
{"title":"The role of DAMP cytotoxic fractions in the immune markers’ disruption in patients with urgent surgical pathology and against the background of post-COVID-19 syndrome","authors":"Elena M. Klimova ,&nbsp;Olena V. Lavinska ,&nbsp;Larisa A. Drozdova","doi":"10.1016/j.imlet.2025.107033","DOIUrl":"10.1016/j.imlet.2025.107033","url":null,"abstract":"<div><h3>Background</h3><div>As a result of the SARS-CoV-2 pandemic, various population groups were formed that had acute and asymptomatic COVID-19. A survey in these groups revealed with equal frequency an asthenic symptom complex, the so-called post-COVID-19 syndrome (PCS). The frequency of urgent surgical pathology against the background of PCS and structural and functional disorders of various organs was increased. The aim – to study the dynamics of immunoresistance factors changes in patients with urgent surgical pathology that developed against the background of PCS and to identify pathogenic markers of the severe course and the risk of mortality.</div></div><div><h3>Materials and methods</h3><div>To examine patients with PCS and urgent cardiovascular (<em>n</em> = 103) and abdominal (<em>n</em> = 106) pathology we used the following methods: fluorescence microscopy, confocal microscopy, flow cytometry, spectrophotometry, ELISA.</div></div><div><h3>Results</h3><div>We revealed a temporal dependence of immune dysfunction in patients with a comorbid course of urgent surgical pathology and PCS. The nature of the DAMP (damage-associated molecular patterns) cytotoxic fractions ratio was associated with certain changes in innate and adaptive immunity factors, severity of the condition and risk of mortality. At the first stage (2020–2021), patients with PCS has disorders of the humoral and cellular components of innate immunity against the background of an increase in the oligopeptide and peptide DAMP fractions. At the second stage (2022–2024) of PCS development, changes in innate as well as adaptive immunity were observed against the background of an increase in the cytotoxic oligonucleotide DAMP fraction (mortality was 17.3 %).</div></div><div><h3>Conclusions</h3><div>The identified markers of impaired immunoresistance in cardiovascular and abdominal urgent pathology can be used to select targeted therapy tactics.</div></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":"276 ","pages":"Article 107033"},"PeriodicalIF":3.3,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144132257","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}
引用次数: 0
Dynactin subunit 1 facilitates mast cell degranulation to drive food allergy pathogenesis Dynactin亚单位1促进肥大细胞脱颗粒驱动食物过敏发病机制。
IF 3.3 4区 医学
Immunology letters Pub Date : 2025-05-20 DOI: 10.1016/j.imlet.2025.107035
Miao Zhao , Hanqing Zhang , Zhiqiang Liu , Jiangqi Liu , Bailing Xie , Lu Zeng , Xiangyu Wang , Qing Shu , Ping Tang , Lihua Mo , Haotao Zeng , Pingchang Yang
{"title":"Dynactin subunit 1 facilitates mast cell degranulation to drive food allergy pathogenesis","authors":"Miao Zhao ,&nbsp;Hanqing Zhang ,&nbsp;Zhiqiang Liu ,&nbsp;Jiangqi Liu ,&nbsp;Bailing Xie ,&nbsp;Lu Zeng ,&nbsp;Xiangyu Wang ,&nbsp;Qing Shu ,&nbsp;Ping Tang ,&nbsp;Lihua Mo ,&nbsp;Haotao Zeng ,&nbsp;Pingchang Yang","doi":"10.1016/j.imlet.2025.107035","DOIUrl":"10.1016/j.imlet.2025.107035","url":null,"abstract":"<div><h3>Background</h3><div>Mast cells play pivotal roles in allergic pathogenesis and inflammatory disorders, with their pathologic effects largely mediated through granule exocytosis. Dynactin subunit 1 (Dctn1), a microtubule-associated motor protein, remains unexplored in mast cell-driven inflammation. This study investigates Dctn1’s functional role in regulating mast cell degranulation during food allergy (FA).</div></div><div><h3>Methods</h3><div>An ovalbumin-sensitized murine FA model was established to profile mast cell activity. Gut lavage fluid (GLF) was analyzed via Olink proteomics and ELISA to quantify Dctn1 levels and mast cell mediators (histamine, Mcpt1). Mechanistic studies employed RNA interference, conditional knockout mice (<em>Dctn1</em><sup>f/f</sup> <em>Cma1</em>-Cre), and immunoprecipitation to assess Dctn1’s role in granule trafficking.</div></div><div><h3>Results</h3><div>FA mice exhibited 3.2-fold higher Dctn1 levels in GLF versus controls (<em>p</em> &lt; 0.001), strongly correlating with mast cell mediator concentrations (histamine: <em>r</em> = 0.73; Mcpt1: <em>r</em> = 0.7). Intestinal mast cells showed selective Dctn1 upregulation (2.8-fold mRNA increase, <em>p</em> &lt; 0.01), mechanistically linked to granule trafficking through CMA1 complex formation. Mast cell-specific Dctn1 ablation reduced Mcpt1 release by 74 % (<em>p</em> &lt; 0.001) and ameliorated FA symptoms (92 % core temperature drop, <em>p</em> &lt; 0.005), independent of AKT/ERK signaling pathways.</div></div><div><h3>Conclusions</h3><div>This study identifies Dctn1 as a novel regulator of mast cell degranulation in FA, operating through microtubule-dependent granule transport. Targeted inhibition of Dctn1 significantly attenuates allergic responses without disrupting canonical activation signals, positioning it as a promising therapeutic target for mast cell-driven pathologies.</div></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":"276 ","pages":"Article 107035"},"PeriodicalIF":3.3,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144127527","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}
引用次数: 0
Attenuated notch signaling decreases T-cell factor-1+ Treg subsets in lung adenocarcinoma, assisting early patient screening 减弱的Notch信号减少了肺腺癌中的t细胞因子-1+ Treg亚群,有助于早期患者筛查。
IF 3.3 4区 医学
Immunology letters Pub Date : 2025-05-20 DOI: 10.1016/j.imlet.2025.107034
Ayibaota Bahabayi , Mohan Zheng , Ainizati Hasimu , Rui Kang , Qi Li , Ziqi Xiong , Zhao Guan , Zhonghui Zhang , Tianci Liu , Xingyue Zeng , Chen Liu
{"title":"Attenuated notch signaling decreases T-cell factor-1+ Treg subsets in lung adenocarcinoma, assisting early patient screening","authors":"Ayibaota Bahabayi ,&nbsp;Mohan Zheng ,&nbsp;Ainizati Hasimu ,&nbsp;Rui Kang ,&nbsp;Qi Li ,&nbsp;Ziqi Xiong ,&nbsp;Zhao Guan ,&nbsp;Zhonghui Zhang ,&nbsp;Tianci Liu ,&nbsp;Xingyue Zeng ,&nbsp;Chen Liu","doi":"10.1016/j.imlet.2025.107034","DOIUrl":"10.1016/j.imlet.2025.107034","url":null,"abstract":"<div><h3>Objective</h3><div>This study aimed to investigate the role of T-cell factor-1 (TCF1) in early-stage lung adenocarcinoma (LUAD) patients and explore its clinical significance for diagnosing early LUAD.</div></div><div><h3>Methods</h3><div>Blood samples were collected from 34 stage IA LUAD patients and 31 healthy controls. Flow cytometry was used to analyze the levels of TCF1 in circulating T cell subpopulations. Functional characteristics of TCF1-related cells were investigated by staining with CD62L and Ki-67. Changes in TCF1-related proportions in T cell subsets of early LUAD patients were analyzed. The role of Notch signaling was clarified by adding the Notch signal activator Jagged1 (JAG1). Receiver operating characteristic (ROC) curves were used to evaluate the diagnostic value of TCF1-related T cell subsets for screening early LUAD.</div></div><div><h3>Results</h3><div>The expression level of TCF1 in follicular regulatory T(Tfr) and regulatory T(Treg) cells was decreased in early LUAD patients, and TCF1+CD62L+ follicular helper (Tfh) cells were also decreased. TCF1+CD62L+ cells in both Treg and Tfr were decreased in early LUAD patients. Decreased TCF1 in Treg and Tfr recovered in early LUAD after adding JAG1. TCF1-related indicators showed good auxiliary diagnostic significance for early LUAD. TCF1+, TCF1+CD62L+, and TCF1-CD62L+ percentages in Treg and Tfr cells were with areas under the curve (AUCs) between 0.827 and 0.897 to distinguish early LUAD from healthy individuals.</div></div><div><h3>Conclusions</h3><div>Downregulation of Notch signaling contributes to the decrease in TCF1+ Treg subsets in LUAD patients, which is of significant value for screening early-stage lung adenocarcinoma.</div></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":"276 ","pages":"Article 107034"},"PeriodicalIF":3.3,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144127504","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}
引用次数: 0
Inhibition of FOSL1 alleviates inflammatory injury of otitis media by reducing ferroptosis 抑制FOSL1可通过减轻铁下垂减轻中耳炎的炎症损伤。
IF 3.3 4区 医学
Immunology letters Pub Date : 2025-05-14 DOI: 10.1016/j.imlet.2025.107032
Zhuohui Liu , Fan Zhang , Fengfeng Jia, Yongmei Yu, Ruiqing Long
{"title":"Inhibition of FOSL1 alleviates inflammatory injury of otitis media by reducing ferroptosis","authors":"Zhuohui Liu ,&nbsp;Fan Zhang ,&nbsp;Fengfeng Jia,&nbsp;Yongmei Yu,&nbsp;Ruiqing Long","doi":"10.1016/j.imlet.2025.107032","DOIUrl":"10.1016/j.imlet.2025.107032","url":null,"abstract":"<div><h3>Objectives</h3><div>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.</div></div><div><h3>Methods</h3><div>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) analyzes 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 <em>Staphylococcus aureus</em> and <em>Bacillus cereus</em> administration<em>.</em> 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.</div></div><div><h3>Results</h3><div>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.</div></div><div><h3>Conclusion</h3><div>FOSL1 inhibition could alleviate release of inflammatory cytokines and ferroptosis in the OM cell model.</div></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":"276 ","pages":"Article 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}
引用次数: 0
Low IL-35 expression in CSF is associated with Neuro-Behcet Disease: Comparative analysis between parenchymal and Non-parenchymal NBD 脑脊液IL-35低表达与神经白塞病相关:实质性与非实质性NBD的比较分析
IF 3.3 4区 医学
Immunology letters Pub Date : 2025-05-11 DOI: 10.1016/j.imlet.2025.107031
Kamel Hamzaoui , FayçalHaj Sassi , Mariem Salhi , Agnès Hamzaoui
{"title":"Low IL-35 expression in CSF is associated with Neuro-Behcet Disease: Comparative analysis between parenchymal and Non-parenchymal NBD","authors":"Kamel Hamzaoui ,&nbsp;FayçalHaj Sassi ,&nbsp;Mariem Salhi ,&nbsp;Agnès Hamzaoui","doi":"10.1016/j.imlet.2025.107031","DOIUrl":"10.1016/j.imlet.2025.107031","url":null,"abstract":"<div><h3>Background</h3><div>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).</div></div><div><h3>Methods</h3><div>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<sup>+</sup> CD25<sup>+</sup> Foxp3<sup>+</sup> 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<sup>−ΔΔCt</sup>. We employed a receiver operating characteristic (ROC) curve to investigate the predictive value of IL-35 levels.</div></div><div><h3>Results</h3><div>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 (<em>p</em> <em>= 0.0001</em>) and protein (<em>p</em> <em>= 0.0004</em>) 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 (<em>r</em> = 0.554, <em>p</em> <em>= 0.0001</em>). Negative associations were observed between Tregs and CRP (<em>r</em> =- 0.518; <em>p</em> <em>= 0.0001</em>) and ESR (<em>r</em> = -0.571; <em>p</em> <em>= 0.0001</em>) 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.</div></div><div><h3>Conclusion</h3><div>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.</div></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":"275 ","pages":"Article 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}
引用次数: 0
Quercetin improves macrophage immune regulatory functions to alleviate airway Th2 polarization 槲皮素改善巨噬细胞免疫调节功能,缓解气道Th2极化
IF 3.3 4区 医学
Immunology letters Pub Date : 2025-04-30 DOI: 10.1016/j.imlet.2025.107030
Yixuan Dong , Le Liu , Xiwen Zhang , Haoyue Zheng , Yu Liu , Aizhi Zhang , Lingzhi Xu , Yuanyi Zhang , Gui Yang , Pingchang Yang
{"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}
引用次数: 0
Platelet-derived microvesicles modulate cytokine and lipid mediator profiles in THP-1 monocytes and macrophages 血小板来源的微泡调节THP-1单核细胞和巨噬细胞的细胞因子和脂质介质谱
IF 3.3 4区 医学
Immunology letters Pub Date : 2025-04-28 DOI: 10.1016/j.imlet.2025.107029
Robert D. Foulem , Maroua Mbarik , Jérémie A. Doiron , Marie-France N. Soucy , Dayana Toro-Ramirez , Florient Pecourt , David A. Barnett , Luc H. Boudreau , Marc E. Surette
{"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 M<sub>0</sub> and M<sub>1</sub> 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 M<sub>1</sub> 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 M<sub>0</sub> cells as well as IL-23 and IL-6 in M<sub>1</sub> macrophages. When stimulated with lipopolysaccharides, PMV-treated M<sub>0</sub> 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}
引用次数: 0
Unveiling the hidden syndrome: The enigma of anti-transcobalamin receptor autoantibodies 揭开隐藏的综合症:抗转钴胺素受体自身抗体之谜
IF 3.3 4区 医学
Immunology letters Pub Date : 2025-04-23 DOI: 10.1016/j.imlet.2025.107028
Kazuki M. Matsuda, Hirohito Kotani, Shinichi Sato, Ayumi Yoshizaki
{"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}
引用次数: 0
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