Immunology letters最新文献

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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
Identification of S100A9 as a target for diagnosis and treatment of Crohn’s Disease after Vedolizumab treatment failure 在Vedolizumab治疗失败后,S100A9作为诊断和治疗克罗恩病的靶点的鉴定
IF 3.3 4区 医学
Immunology letters Pub Date : 2025-04-23 DOI: 10.1016/j.imlet.2025.107027
Yanru Zhang , Zhe Zhang , Ruixian Liu, Yijia He, Shiyang Ning, Junzhi Yu, Yan Liu, Yimeng Xia, Xinji Pang, Wen Lv, Qiankun Sun, Yilong Li, Zhihong Wang, Lu Liu, Baisui Feng
{"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}
引用次数: 0
NETs activate AIM2 to mediate synovial fibroblast pyroptosis and promote acute gouty arthritis development net激活AIM2介导滑膜成纤维细胞焦亡,促进急性痛风性关节炎的发展
IF 3.3 4区 医学
Immunology letters Pub Date : 2025-04-22 DOI: 10.1016/j.imlet.2025.107007
Jing Tian , Ying Liu , Wei Gao , Xiuyun Shi , Feng Cheng , Bing Xie
{"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}
引用次数: 0
Mast cell activation signature as a potential biomarker in COVID-19 肥大细胞激活特征作为COVID-19的潜在生物标志物
IF 3.3 4区 医学
Immunology letters Pub Date : 2025-04-16 DOI: 10.1016/j.imlet.2025.107026
Yatsiri G. Meneses-Preza , Rodolfo Soria-Castro , Ángel R. Alfaro-Doblado , Alejandro Hernández-Solis , Pablo Álvarez-Maldonado , Diana Gómez-Martín , Jiram Torres-Ruiz , José Francisco Muñoz-Valle , Guillermina Muñoz-Ríos , Cristian Oswaldo Hernández-Ramírez , Azmavet M. Güemes-González , Isabel Wong-Baeza , José Luis Maravillas-Montero , Sonia M. Pérez-Tapia , Alma D. Chávez-Blanco , Sergio Estrada-Parra , Rommel Chacón-Salinas
{"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}
引用次数: 0
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