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, Jingli Liu, Liuling Chen, Ruying Li, Jinpin Li","doi":"10.1016/j.imlet.2025.107050","DOIUrl":"https://doi.org/10.1016/j.imlet.2025.107050","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":" ","pages":"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}
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, Nataša Radulović, Simonida Bobić, Sandra Radenković, Aránzazu Cruz-Adalia, Ivana Stojanović","doi":"10.1016/j.imlet.2025.107051","DOIUrl":"https://doi.org/10.1016/j.imlet.2025.107051","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":" ","pages":"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}
{"title":"Human keratinocytes exposed to a clinical strain of Leishmania tropica can result in parasite internalization.","authors":"Imane El Idrissi Saik, Borja Prat-Luri, Yazmin Hauyon-La Torre, Meryem Lemrani, Myriam Riyad, Fabienne Tacchini-Cottier","doi":"10.1016/j.imlet.2025.107049","DOIUrl":"https://doi.org/10.1016/j.imlet.2025.107049","url":null,"abstract":"<p><p>Cutaneous Leishmaniasis (CL) due to Leishmania tropica 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. tropica 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 Leishmania 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 Leishmania species, influencing disease outcomes and helping create a unique microenvironment tailored to each species, thus affecting disease progression. Herein, we have conducted in vitro infection of the human keratinocytes HaCaT cell line with Moroccan clinical strains of L. tropica and L. major. Through flow cytometry and imaging flow cytometry, we show that keratinocytes are infected with both Leishmania species and that they internalize L. tropica parasites. We also report that infection with L. tropica exhibits a higher infection frequency in keratinocytes compared to L. major. 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. tropica and opens new perspectives for research into CL-specific skin immune mechanisms.</p>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":" ","pages":"107049"},"PeriodicalIF":3.3,"publicationDate":"2025-06-07","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}
{"title":"The emerging role of GlycoRNAs in immune regulation and recognition","authors":"Nicole Montag , Pavlos Gousis , 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}
{"title":"DUSP14 attenuates airway inflammation and mucus hypersecretion in allergic asthma by regulating TAK1 activity","authors":"Rui Kong , Jun Bai , Qing Yao , 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}
{"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, 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 >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}
{"title":"Increased expression of membrane-bound TGF-β1, GITR, and GITR ligand in patients with autoimmune thyroid disease","authors":"Fumiaki Hayashi , Naoya Inoue , Yoshinori Iwatani , Yuka Yamashita , Hiroya Yamada , Akira Miyauchi , 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}
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 , Olena V. Lavinska , 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}
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 , Hanqing Zhang , Zhiqiang Liu , Jiangqi Liu , Bailing Xie , Lu Zeng , Xiangyu Wang , Qing Shu , Ping Tang , Lihua Mo , Haotao Zeng , 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> < 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> < 0.01), mechanistically linked to granule trafficking through CMA1 complex formation. Mast cell-specific Dctn1 ablation reduced Mcpt1 release by 74 % (<em>p</em> < 0.001) and ameliorated FA symptoms (92 % core temperature drop, <em>p</em> < 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}
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 , Mohan Zheng , Ainizati Hasimu , Rui Kang , Qi Li , Ziqi Xiong , Zhao Guan , Zhonghui Zhang , Tianci Liu , Xingyue Zeng , 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}