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Reactive oxygen species production by monocytes negatively correlates with disease activity in rheumatoid arthritis 类风湿关节炎中单核细胞活性氧的产生与疾病活动性呈负相关。
IF 3.3 4区 医学
Immunology letters Pub Date : 2025-06-08 DOI: 10.1016/j.imlet.2025.107052
Pablo Lores , Monique Costa , Anderson Saravia , Mercedes Landeira , Valeria da Costa , Santiago A. Rodríguez-Zraquia , M. Eugenia Cedrés , Juan Oliva , Guillermina Rado , Ignacio García , M. Florencia Festari , Sandra Consani , Carolina Díaz , Teresa Freire
{"title":"Reactive oxygen species production by monocytes negatively correlates with disease activity in rheumatoid arthritis","authors":"Pablo Lores ,&nbsp;Monique Costa ,&nbsp;Anderson Saravia ,&nbsp;Mercedes Landeira ,&nbsp;Valeria da Costa ,&nbsp;Santiago A. Rodríguez-Zraquia ,&nbsp;M. Eugenia Cedrés ,&nbsp;Juan Oliva ,&nbsp;Guillermina Rado ,&nbsp;Ignacio García ,&nbsp;M. Florencia Festari ,&nbsp;Sandra Consani ,&nbsp;Carolina Díaz ,&nbsp;Teresa Freire","doi":"10.1016/j.imlet.2025.107052","DOIUrl":"10.1016/j.imlet.2025.107052","url":null,"abstract":"<div><div>Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by severe joint inflammation, synovial hyperplasia and degradation of the cartilage and bone in the joint. Patients with RA have an amplified T helper (Th) 1 and Th17 immune response and production of autoantibodies by autoreactive B cells. In the joint, macrophages mediate bone destruction and maintain the inflammatory process in RA. There is an increasing body of evidence indicating that NADPH oxidase (NOX2)-derived reactive oxygen species (ROS), mainly produced by macrophages and neutrophils, may have effector functions in RA.</div><div>In this work we characterized ROS production in both monocytes and macrophages in RA. Our results indicate that NOX2-dependent production of ROS attenuates inflammation and clinical signs by decreasing innate and adaptive immune responses in collagen-induced arthritis in mice. We also report that ROS production by circulating classical and non-classical monocytes from patients with RA negatively correlate with disease symptoms. Therefore, ROS produced by different monocyte subsets in peripheral blood might be considered as useful biomarkers or predictors of the immune response associated with RA disease activity.</div></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":"276 ","pages":"Article 107052"},"PeriodicalIF":3.3,"publicationDate":"2025-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144266079","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
Human keratinocytes exposed to a clinical strain of Leishmania tropica can result in parasite internalization 人类角化细胞暴露于热带利什曼原虫临床菌株可导致寄生虫内化。
IF 3.3 4区 医学
Immunology letters Pub Date : 2025-06-08 DOI: 10.1016/j.imlet.2025.107049
Imane El Idrissi Saik , Borja Prat-Luri , Yazmin Hauyon-La Torre , Meryem Lemrani , Myriam Riyad , Fabienne Tacchini-Cottier
{"title":"Human keratinocytes exposed to a clinical strain of Leishmania tropica can result in parasite internalization","authors":"Imane El Idrissi Saik ,&nbsp;Borja Prat-Luri ,&nbsp;Yazmin Hauyon-La Torre ,&nbsp;Meryem Lemrani ,&nbsp;Myriam Riyad ,&nbsp;Fabienne Tacchini-Cottier","doi":"10.1016/j.imlet.2025.107049","DOIUrl":"10.1016/j.imlet.2025.107049","url":null,"abstract":"<div><div>Cutaneous Leishmaniasis (CL) due to <em>Leishmania tropica</em> is a public health burden in Morocco. The increasing clinical polymorphism challenges its proper diagnosis and treatment. Although the immunopathogenesis of CL due to L. <em>tropica</em> has been documented, the role of keratinocytes, a critical cell type in skin immunity, has never been investigated in this pathology. Overall, keratinocytes play a crucial role in the recognition and early immune response to <em>Leishmania</em> parasites upon skin inoculation, influencing the local immune response by producing early cytokines that shape anti-leishmanial immune responses. Moreover, they respond differently to each <em>Leishmania</em> species, influencing disease outcomes and helping create a unique microenvironment tailored to each species, thus affecting disease progression.</div><div>Herein, we have conducted <em>in vitro</em> infection of the human keratinocytes HaCaT cell line with Moroccan clinical strains of L. <em>tropica</em> and L. <em>major</em>. Through flow cytometry and imaging flow cytometry, we show that keratinocytes are infected with both <em>Leishmania</em> species and that they internalize L. <em>tropica</em> parasites. We also report that infection with L. <em>tropica</em> exhibits a higher infection frequency in keratinocytes compared to L. <em>major</em>. These findings support the potential involvement of keratinocytes in the early stages of cutaneous infection. However, further investigations are required to elucidate their role in modulating the local immune response. Our study is a first step in the investigation of keratinocytes involvement during CL due to L. <em>tropica</em> and opens new perspectives for research into CL-specific skin immune mechanisms.</div></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":"276 ","pages":"Article 107049"},"PeriodicalIF":3.3,"publicationDate":"2025-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144258009","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
miR-125a-5p regulates Treg function by targeting Foxp3 in experimental autoimmune myasthenia gravis mice miR-125a-5p通过靶向Foxp3调控实验性自身免疫性重症肌无力小鼠Treg功能
IF 3.3 4区 医学
Immunology letters Pub Date : 2025-06-07 DOI: 10.1016/j.imlet.2025.107050
Shuting Tan, Jingli Liu, Liuling Chen, Ruying Li, Jinpin Li
{"title":"miR-125a-5p regulates Treg function by targeting Foxp3 in experimental autoimmune myasthenia gravis mice","authors":"Shuting Tan,&nbsp;Jingli Liu,&nbsp;Liuling Chen,&nbsp;Ruying Li,&nbsp;Jinpin Li","doi":"10.1016/j.imlet.2025.107050","DOIUrl":"10.1016/j.imlet.2025.107050","url":null,"abstract":"<div><div>MicroRNAs are a class of endogenous noncoding small RNAs. miR-125a-5p is involved in immunoregulatory mechanisms in autoimmune diseases. Myasthenia gravis (MG) is an autoimmune disease in which regulatory T cells (Tregs) exhibit reduced numbers and functional defects, with decreased expression of the Treg cell-specific transcription factor Foxp3. Our previous study identified an abnormally high expression of miR-125a-5p in thymoma-associated myasthenia gravis, however, the involvement of miR-125a-5p in the pathogenesis of myasthenia gravis in vivo is unclear. In this study, we explored the role of thymic miR-125a-5p abnormalities in the pathogenesis of myasthenia gravis by establishing an experimental autoimmune myasthenia gravis model. Muscle strength score, low-frequency repetitive nerve stimulation, and serum acetylcholine receptor antibody were performed. The relative expression of miR-125a-5p and Foxp3 in the thymus and spleen was quantified, and the percentage of Treg cells, the levels of the inhibitory cytokines IL-10 and TGF-β1, and the proliferative capacity of splenic T lymphocytes were detected. Our findings revealed significant upregulation of miR-125a-5p expression in myasthenia gravis models. Reducing miR-125a-5p levels alleviated muscle weakness symptoms, elevated Foxp3 expression, enhanced the number of Treg cells, elevated the levels of the Treg-associated inhibitory cytokines IL-10 and TGF-β1, and inhibited the proliferative function of splenic T lymphocytes. The opposite result was obtained when miR-125a-5p was overexpressed. These results suggest that miR-125a-5p can inhibit Foxp3 expression, leading to a decrease in the number and abnormal function of Treg cells. Thus, our findings suggest that miR-125a-5p participates in the pathogenesis of myasthenia gravis by targeting Foxp3 to regulate the function of Treg cells, providing new insights to explore the immunoregulatory mechanisms of miR-125a-5p in myasthenia gravis.</div></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":"276 ","pages":"Article 107050"},"PeriodicalIF":3.3,"publicationDate":"2025-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144257927","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
Innate lymphoid cells: Dual roles and therapeutic opportunities in breast cancer 先天淋巴样细胞:乳腺癌的双重作用和治疗机会。
IF 3.3 4区 医学
Immunology letters Pub Date : 2025-06-07 DOI: 10.1016/j.imlet.2025.107051
Marija Mojić , Nataša Radulović , Simonida Bobić , Sandra Radenković , Aránzazu Cruz-Adalia , Ivana Stojanović
{"title":"Innate lymphoid cells: Dual roles and therapeutic opportunities in breast cancer","authors":"Marija Mojić ,&nbsp;Nataša Radulović ,&nbsp;Simonida Bobić ,&nbsp;Sandra Radenković ,&nbsp;Aránzazu Cruz-Adalia ,&nbsp;Ivana Stojanović","doi":"10.1016/j.imlet.2025.107051","DOIUrl":"10.1016/j.imlet.2025.107051","url":null,"abstract":"<div><div>Innate lymphoid cells (ILC) play a crucial role in shaping immune responses and maintaining tissue homeostasis. Recent research has identified their involvement in breast cancer pathogenesis, mainly through shaping the tumor microenvironment, where they can exert dual roles, either promoting tumor eradication by enhancing anti-tumor immunity, or facilitating tumor progression through mechanisms of immune evasion. This functional plasticity makes ILC attractive targets for immunotherapy. Furthermore, their slow proliferation enables them to survive anti-proliferative radiation therapy and chemotherapy, which may support continuous immune surveillance of breast cancer tissue. However, this same resilience poses a significant challenge, as surviving ILC could contribute to tumor persistence or recurrence. Additionally, anti-estrogen therapy, chemotherapy and immune checkpoint inhibitors, commonly used in breast cancer treatment, may interfere with ILC function, either dampening their anti-tumor potential or enhancing their pro-tumor activities. Understanding the complex interactions between ILC and conventional therapies is critical for designing effective immunotherapeutic approaches that include ILC targeting, potentially overcoming resistance and improving patient outcomes in breast cancer therapy.</div></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":"276 ","pages":"Article 107051"},"PeriodicalIF":3.3,"publicationDate":"2025-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144258010","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 emerging role of GlycoRNAs in immune regulation and recognition 糖rna在免疫调节和识别中的新作用。
IF 3.3 4区 医学
Immunology letters Pub Date : 2025-05-30 DOI: 10.1016/j.imlet.2025.107048
Nicole Montag , Pavlos Gousis , Jürgen Wittmann
{"title":"The emerging role of GlycoRNAs in immune regulation and recognition","authors":"Nicole Montag ,&nbsp;Pavlos Gousis ,&nbsp;Jürgen Wittmann","doi":"10.1016/j.imlet.2025.107048","DOIUrl":"10.1016/j.imlet.2025.107048","url":null,"abstract":"<div><div>Glycosylation, the enzymatic attachment of glycans to biomolecules, is a vital post-translational modification that impacts protein stability, immune recognition, and cellular communication. Traditionally associated with proteins and lipids, recent discoveries have revealed the existence of glycosylated RNAs (glycoRNAs), expanding our understanding of RNA modifications. GlycoRNAs challenge conventional paradigms by suggesting that glycosylation may regulate RNA stability, localization, and interactions with glycan-binding proteins, such as sialic acid-binding immunoglobulin-type lectins (Siglecs) and selectins. These interactions are particularly significant in the immune system, where glycosylation plays a key role in antigen recognition, immune cell trafficking, and pathogen detection.</div><div>The potential implications of glycoRNAs in immune regulation and disease are profound, with roles in autoimmune disorders, cancer, and infectious diseases. Advances in glycobiology, including mass spectrometry, RNA sequencing, glycan microarrays, and click chemistry technologies, are driving the growth of glycoRNA research and its translational applications. Understanding glycoRNAs could lead to new therapeutic opportunities, including glycoengineering, biomarker discovery, and targeted immune interventions. Despite challenges including low abundance and complex structure, research into glycoRNA is progressing rapidly, revealing their roles in immune responses and disease mechanisms. This review synthesizes the current knowledge on glycoRNAs, highlighting their emerging significance in immunology and outlining future research directions.</div></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":"276 ","pages":"Article 107048"},"PeriodicalIF":3.3,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144198968","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
DUSP14 attenuates airway inflammation and mucus hypersecretion in allergic asthma by regulating TAK1 activity DUSP14通过调节TAK1活性减轻变应性哮喘气道炎症和粘液高分泌。
IF 3.3 4区 医学
Immunology letters Pub Date : 2025-05-29 DOI: 10.1016/j.imlet.2025.107047
Rui Kong , Jun Bai , Qing Yao , Xiaoqing Xu
{"title":"DUSP14 attenuates airway inflammation and mucus hypersecretion in allergic asthma by regulating TAK1 activity","authors":"Rui Kong ,&nbsp;Jun Bai ,&nbsp;Qing Yao ,&nbsp;Xiaoqing Xu","doi":"10.1016/j.imlet.2025.107047","DOIUrl":"10.1016/j.imlet.2025.107047","url":null,"abstract":"<div><div>Allergic asthma is characterized by persistent chronic airway inflammation, leading to mucus hypersecretion and airway hyperresponsiveness. Dual-specificity phosphatase 14 (DUSP14), a member of the DUSP family, is a key regulator in various biological processes. However, the function of DUSP14 in allergic asthma remains to be elucidated. In this study, we aim to explore the function and mechanism of DUSP14 in asthma-related airway inflammation. In an ovalbumin (OVA) asthma mouse model, DUSP14 was found to be significantly diminished. DUSP14 overexpression relieved airway inflammation and attenuated airway mucus production. <em>In vitro</em>, overexpression of DUSP14 attenuated IL-13-induced cellular inflammation and mucus hypersecretion in bronchial epithelial cells (BEAS-2B). Afterwards, we used the co-immunoprecipitation assay to confirm that DUSP14 interacted with TAK1. DUSP14 overexpression restrained the activation of TAK1 and NF-κB signaling pathway <em>in vitro</em> and <em>in vivo</em>. Taken together, our findings clearly showed that DUSP14 could alleviate airway inflammation by inhibiting TAK1 activity and NF-κB signaling pathway, positioning the DUSP14-TAK1-NF-κB regulatory axis as a potential therapeutic target for allergic asthma.</div></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":"276 ","pages":"Article 107047"},"PeriodicalIF":3.3,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144191729","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
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
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