ImmunologyPub Date : 2025-04-23DOI: 10.1111/imm.13934
Gustavo Gastão Davanzo, Bianca Gazieri Castelucci, Gabriela Fabiano de Souza, Stéfanie Primon Muraro, Larissa Menezes Dos Reis, Isabella Bonilha de Oliveira, José Luís Fachi, João Victor Virgilio-da-Silva, Marcelo Rodrigues Berçot, Mariane Font Fernandes, Sarah de Oliveira, Nathalia Vitoria Pereira Araujo, Guilherme Ribeiro, Gisele de Castro, Webster Leonardo Guimarães Costa, Adriana Leandra Santoro, Gabriela Flavia Rodrigues-Luiz, Helison Rafael P do Carmo, Ikaro Breder, Marcelo A Mori, Alessandro S Farias, Daniel Martins-de-Souza, Joseph W Guarnieri, Douglas C Wallace, Marco Aurélio Ramirez Vinolo, José Luiz Proença-Módena, Afshin Beheshti, Andrei C Sposito, Pedro M Moraes-Vieira
{"title":"Obesity-Induced Metabolic Priming Exacerbates SARS-CoV-2 Inflammation.","authors":"Gustavo Gastão Davanzo, Bianca Gazieri Castelucci, Gabriela Fabiano de Souza, Stéfanie Primon Muraro, Larissa Menezes Dos Reis, Isabella Bonilha de Oliveira, José Luís Fachi, João Victor Virgilio-da-Silva, Marcelo Rodrigues Berçot, Mariane Font Fernandes, Sarah de Oliveira, Nathalia Vitoria Pereira Araujo, Guilherme Ribeiro, Gisele de Castro, Webster Leonardo Guimarães Costa, Adriana Leandra Santoro, Gabriela Flavia Rodrigues-Luiz, Helison Rafael P do Carmo, Ikaro Breder, Marcelo A Mori, Alessandro S Farias, Daniel Martins-de-Souza, Joseph W Guarnieri, Douglas C Wallace, Marco Aurélio Ramirez Vinolo, José Luiz Proença-Módena, Afshin Beheshti, Andrei C Sposito, Pedro M Moraes-Vieira","doi":"10.1111/imm.13934","DOIUrl":"https://doi.org/10.1111/imm.13934","url":null,"abstract":"<p><p>Despite the early recognition that individuals living with obesity are more prone to develop adverse outcomes during COVID-19, the mechanisms underlying these conditions are still unclear. During obesity, an accumulation of free fatty acids (FFAs) in the circulation promotes low-grade inflammation. Here, we show that FFAs induce epigenetic reprogramming of monocytes, exacerbating their inflammatory profile after SARS-CoV-2 infection, a mechanism named metabolic-primed immunity. Monocytes from people with obesity or primed with palmitate, a central component of circulating FFAs, presented elevated viral load and higher gene expression of IL-6. Palmitate-primed monocytes upregulate fatty acid oxidation and FFAs entry into the mitochondria. FFA-derived acetyl-CoA is then converted into citrate, exiting the mitochondria and is used to support H3K18 histone acetylation, which regulates IL-6 accessibility. Ingestion of palm oil by lean and healthy individuals increased circulating FFAs levels and was sufficient to exacerbate the inflammatory profile of monocytes upon SARS-CoV-2 infection. Our findings demonstrate that obesity-derived FFAs induce the metabolic priming of monocytes, which exacerbates the inflammatory response observed in people with severe COVID-19.</p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144005788","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ImmunologyPub Date : 2025-04-22DOI: 10.1111/imm.13931
Tsz Kin Suen, Burcu Al, Thomas Ulas, Nico Reusch, Harsh Bahrar, Siroon Bekkering, Jaydeep Bhat, Dieter Kabelitz, Joachim L Schultze, Frank L van de Veerdonk, Jeanine Roeters van Lennep, Niels P Riksen, Leo A B Joosten, Mihai G Netea, Katarzyna Placek
{"title":"Human γδ T Cell Function Is Impaired Upon Mevalonate Pathway Inhibition.","authors":"Tsz Kin Suen, Burcu Al, Thomas Ulas, Nico Reusch, Harsh Bahrar, Siroon Bekkering, Jaydeep Bhat, Dieter Kabelitz, Joachim L Schultze, Frank L van de Veerdonk, Jeanine Roeters van Lennep, Niels P Riksen, Leo A B Joosten, Mihai G Netea, Katarzyna Placek","doi":"10.1111/imm.13931","DOIUrl":"https://doi.org/10.1111/imm.13931","url":null,"abstract":"<p><p>Vδ2 T cells, a predominant human peripheral γδ T cell population, are a promising candidate for the development of immunotherapies against cancer and infected cells. Aminobisphosphonate drugs, such as zoledronate, are commonly used to expand Vδ2 T cells. Yet, such in vitro generated cells have limited efficacy in the clinic. We found that despite inducing excessive proliferation of Vδ2 T cells, zoledronate impaired their effector function and caused the upregulation of the inhibitory receptor TIM3. This effect was due to the inhibition of mevalonate metabolism and dysregulation of downstream biological processes such as protein prenylation and intracellular signalling. In vitro and in vivo inhibition of mevalonate metabolism with zoledronate, statins, and 6-fluoromevalonate, as well as genetic deficiency of the mevalonate kinase, all resulted in compromised cytokine and cytotoxic molecule production by Vδ2 T cells. Impaired Vδ2 T cell function was accompanied by transcriptome and kinome changes. Our findings reveal the importance of mevalonate metabolism for the proper functioning of Vδ2 T cells. This observation provides important considerations for improving their therapeutic use and has repercussions for patients with statin or aminobisphosphonate treatments.</p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143984802","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ImmunologyPub Date : 2025-04-17DOI: 10.1111/imm.13930
Christina Antoniadou, Anastasia-Maria Natsi, Dimitrios C Mastellos, Evangelos Papadimitriou, Efstratios Gavriilidis, Victoria Tsironidou, Vasileios Papadopoulos, Evgenios Eftalitsidis, Μaria Κoffa, Markus Huber-Lang, Antonio M Risitano, Despina Yancopoulou, Georgios Germanidis, Konstantinos Ritis, John D Lambris, Panagiotis Skendros
{"title":"Clinical C3 Inhibition With AMY-101 Reveals Novel Insights Into IL-8-Driven Inflammation in COVID-19.","authors":"Christina Antoniadou, Anastasia-Maria Natsi, Dimitrios C Mastellos, Evangelos Papadimitriou, Efstratios Gavriilidis, Victoria Tsironidou, Vasileios Papadopoulos, Evgenios Eftalitsidis, Μaria Κoffa, Markus Huber-Lang, Antonio M Risitano, Despina Yancopoulou, Georgios Germanidis, Konstantinos Ritis, John D Lambris, Panagiotis Skendros","doi":"10.1111/imm.13930","DOIUrl":"https://doi.org/10.1111/imm.13930","url":null,"abstract":"","PeriodicalId":13508,"journal":{"name":"Immunology","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143984839","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The Contribution of Complement System in Multiple Sclerosis: Mechanisms and Therapeutic Potentials.","authors":"Runjing Cao, Li-Wen Zhu, Bo Chen, Huadong Wu, Yifan Cheng, Shunyuan Guo","doi":"10.1111/imm.13929","DOIUrl":"https://doi.org/10.1111/imm.13929","url":null,"abstract":"<p><p>The complement system has been described as playing key roles in both innate and adaptive immune responses. Multiple sclerosis (MS) is an autoimmune disease characterised by the destruction of myelinated axons in the central nervous system (CNS). In this review, we will discuss the possible role of the complement system in MS. Complement components have been found to be highly expressed in post-mortem brains and in blood and cerebrospinal fluid samples of MS patients. Though the use of knock-out mouse models, the specific roles of complement components have been further investigated. According to these studies, complement components have been found to play controversial roles in the pathogenesis of MS. We will discuss the roles of classical and alternative pathways, as well as the lectin pathway, of the complement system in MS. Anaphylatoxins including C3a and C5a were also found to contribute to the pathology of MS. In addition, studies regarding the complement components in blood and cerebrospinal fluid are presented, which may be useful for the prediction and assessment of MS as biomarkers. Overall, this review summarises the importance of the complement system's involvement in the pathology of MS, which may guide future therapeutic approaches to MS and provide potential biomarkers for MS diagnosis and prognosis.</p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143963476","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ImmunologyPub Date : 2025-04-14DOI: 10.1111/imm.13928
Alonso D Cruz-Cruz, Jocelyn C Pérez-Lara, Diana Z Velázquez, Gabriela Hernández-Galicia, Vianney Ortiz-Navarrete
{"title":"B Cells as a Host of Persistent Salmonella Typhimurium.","authors":"Alonso D Cruz-Cruz, Jocelyn C Pérez-Lara, Diana Z Velázquez, Gabriela Hernández-Galicia, Vianney Ortiz-Navarrete","doi":"10.1111/imm.13928","DOIUrl":"https://doi.org/10.1111/imm.13928","url":null,"abstract":"<p><p>Salmonella enterica serovar Typhimurium (S. Tm) can colonise different intracellular niches, either actively dividing or remaining dormant to persist. Bacterial persisters are phenotypic variants that temporarily enter a nonreplicative state. This allows them to evade host cell defences and antibiotics, leading to chronic infections. We previously reported that during chronic periods, Salmonella remains within B cells in the bone marrow and spleen. However, the dynamics of Salmonella replication and the formation of antibiotic tolerance in infected B cells have not been studied. Here we show that B cells are a favourable reservoir for bacterial persistence. In vitro and in vivo experiments identified non-replicating, persistent Salmonella subsets in splenic B cells. These non-replicative Salmonella are tolerant to antibiotics (cefotaxime and ciprofloxacin), while replicative bacteria remain susceptible. Infected mice demonstrated viable, nonreplicative Salmonella in spleen B cells, maintaining antibiotic tolerance. Although acid intravacuolar pH and SPI-2 regulators (SsrA/SsrB) are not necessary for Salmonella persistence in B cells, the SehA/B and RelE/B toxin-antitoxin system facilitates the formation of the persistent phenotype in Salmonella. Overall, we show that B cells are a reservoir for nonreplicating, antibiotic-tolerant Salmonella.</p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144009777","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"SAA1 as a Potential Early Diagnostic Biomarker for Sepsis Through Integrated Proteomics and Metabolomics.","authors":"Mengyao Yuan, Pengfei Huang, Yuhan Liu, Lifeng Shen, Chuanchuan Nan, Yuchen Song, Yu Xiao, Yuxin Zhang, Yuxin Zhou, Yu Xin, Yanqi Liu, Hongxu Li, Yinghao Luo, Qianqian Zhang, Xinran Wang, Dawei Wang, Jiannan Zhang, Likun Zhang, Mingyan Zhao, Kaijiang Yu, Changsong Wang","doi":"10.1111/imm.13925","DOIUrl":"https://doi.org/10.1111/imm.13925","url":null,"abstract":"<p><p>Sepsis is characterised by fatal organ dysfunction resulting from a dysfunctional host response to infection, imposing a substantial economic burden on families and society. Therefore, identifying biomarkers for early sepsis diagnosis and improving patient prognosis are critical. This study recruited 59 sepsis patients and 35 healthy volunteers from the Department of Critical Care Medicine at Harbin Medical University Affiliated First Hospital between March and December 2021. Through a combination of non-targeted and targeted proteomics and metabolomics sequencing, along with various analytical methods, we initially identified and validated serum amyloid A1 (SAA1) as a diagnostic biomarker for sepsis. Our study found that SAA1 was significantly elevated in the sepsis group, demonstrating its diagnostic value for sepsis (AUC: 0.95, 95% CI: 0.88-1). Additionally, a positive correlation was observed between SAA1 and disease severity, as indicated by the Sequential Organ Failure Assessment (SOFA) score (R = 0.51, p = 0.004) and Acute Physiology and Chronic Health Evaluation II (APACHE II) score (R = 0.52, p = 0.003). This study suggests that SAA1 is a potentially effective and reliable marker for diagnosing sepsis and predicting its severity.</p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144004687","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ImmunologyPub Date : 2025-04-04DOI: 10.1111/imm.13923
Stefano Ruberto, Alfredo Santovito, Gian P Caviglia, Marta Noli, Davide Cossu, Davide G Ribaldone, Demis Pitoni, Simona Frara, Elisa Tribocco, Chiara Rosso, Marta Guriglia, Ilaria Cossu, Pier A Tovo, Massimiliano Bergallo, Leonardo A Sechi
{"title":"Mycobacterium avium Subsp. paratuberculosis and Human Endogenous Retrovirus in Italian Patients With Inflammatory Bowel Disease (IBD) and Irritable Bowel Syndrome (IBS).","authors":"Stefano Ruberto, Alfredo Santovito, Gian P Caviglia, Marta Noli, Davide Cossu, Davide G Ribaldone, Demis Pitoni, Simona Frara, Elisa Tribocco, Chiara Rosso, Marta Guriglia, Ilaria Cossu, Pier A Tovo, Massimiliano Bergallo, Leonardo A Sechi","doi":"10.1111/imm.13923","DOIUrl":"https://doi.org/10.1111/imm.13923","url":null,"abstract":"<p><p>Inflammatory bowel disease (IBD), comprising ulcerative colitis (UC) and Crohn's disease (CD) and irritable bowel syndrome (IBS) are distinct gastrointestinal disorders. Mycobacterium avium subspecies paratuberculosis (MAP) is implicated in IBD pathogenesis, while the roles of human endogenous retroviruses (HERVs) are under investigation. We aimed (a) to investigate whether the levels of humoral response to MAP-3865c, HERV-K envelope and HERV-W envelope against the epitopes in IBD/IBS patients; (b) to determine the frequency of micronuclei in IBD patients and (c) to evaluate the possible correlation between genomic damage and humoral response. This study investigates antibody titres against MAP 3865c, HERV-K env and HERV-W env in plasma from 102 IBD, 20 IBS patients and 92 healthy controls (HCs). Micronuclei (MNi) frequency in IBD patients is assessed, correlating with humoral responses and patient genotype profiles. IBD patients exhibited elevated antibody responses to MAP 3865c, with those carrying the GA genotype for TNF-α showing higher anti-MAP 3865c IgG levels. A significant positive correlation was observed between MNi frequency and the humoral response against MAP 3865c in IBD patients. Higher antibody responses to HERV-K env were detected in both IBD and IBS patients compared to HCs, with significant positive correlations found between MAP 3865c and HERV-K env peptide responses in IBD patients. HERV-W env antibody levels were higher in IBS patients than in HCs. Our findings highlight the association between UC and CD and immune responses targeting MAP and HERV-Kenv. Specific genetic profiles may exacerbate inflammation, potentially amplifying genetic damage observed in IBD patients, as indicated by MNi frequencies.</p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143780043","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ImmunologyPub Date : 2025-03-26DOI: 10.1111/imm.13926
Ignazio Piseddu, Jan Gärtig, Stephan Eiber, Stefan Moder, Raffael Thaler, Matthias Thaler, Juliane Gruen, Marlies Vornhülz, Kevin Bahner, Luana Messa, Benjamin Kühnemuth, Jennifer Müller, Konstantin Schnell, Antonia Beimert, Carolin Perleberg, Natascha Röhrle, Maximilian Martin Ludwig Knott, Linda Hammann, Vanessa Wittmann, Patrick Layritz, Moritz Rapp, Carole Bourquin, Julia Mayerle, Stefan Endres, David Anz
{"title":"Innate Immune Activation Is a Strong Suppressor of CCL22 and Impedes Regulatory T Cell-Dendritic Cell Interaction.","authors":"Ignazio Piseddu, Jan Gärtig, Stephan Eiber, Stefan Moder, Raffael Thaler, Matthias Thaler, Juliane Gruen, Marlies Vornhülz, Kevin Bahner, Luana Messa, Benjamin Kühnemuth, Jennifer Müller, Konstantin Schnell, Antonia Beimert, Carolin Perleberg, Natascha Röhrle, Maximilian Martin Ludwig Knott, Linda Hammann, Vanessa Wittmann, Patrick Layritz, Moritz Rapp, Carole Bourquin, Julia Mayerle, Stefan Endres, David Anz","doi":"10.1111/imm.13926","DOIUrl":"https://doi.org/10.1111/imm.13926","url":null,"abstract":"<p><p>The chemokine CCL22 is constitutively expressed at high levels in lymphoid organs, where it controls immunity by promoting contacts between dendritic cells (DC) and regulatory T cells (Treg). However, its regulation and impact in the context of pattern recognition receptor (PRR) stimulation and microbial infection are unknown. Here we show that CCL22 levels in lymphoid organs of mice were strongly suppressed upon stimulation with TLR agonists. In vitro, activation of Toll-like receptors (TLR), RIG-I like helicases (RLH) and stimulator of interferon genes (STING) resulted in a potent downregulation of CCL22. Mechanistically, the suppression of DC-derived CCL22 secretion was exerted by inflammatory cytokines such as IFN-α, IFN-γ and IL-10 released upon TLR activation by B and T cells. Decreased CCL22 synthesis correlated with reduced frequencies of cellular clustering between Treg and DC in co-cultures. CCL22 suppression was also observed upon microbial infection, since CCL22 levels were significantly reduced in lymphoid organs of mice upon injection of Salmonella typhimurium. As a clinical correlate, CCL22 serum concentrations were decreased in patients with sepsis compared to controls. Taken together, we demonstrate a strong and long-lasting suppression of CCL22 as a consequence of innate immune activation. In the context of microbial infection, transient reduction of CCL22 reduces Treg-DC interactions and may thereby represent a mechanism to weaken Treg function in order to enable an effective immune response and pathogen clearance.</p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143709756","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Targeting Immune Cell Metabolism: A Promising Therapeutic Approach for Cardiovascular Disease","authors":"Dexiang Xia, Qinwen Zheng, Yue Liu, Lihua Wang, Dangheng Wei","doi":"10.1111/imm.13913","DOIUrl":"10.1111/imm.13913","url":null,"abstract":"<p>Cardiovascular disease (CVD) is a leading cause of morbidity and mortality globally. Recent groundbreaking preclinical and clinical research underscores the pivotal role of metabolite remodelling in the pathology of CVD. This metabolic transformation not only directly fuels the progression of CVD but also profoundly influences the immune response within the cardiovascular system. In this review, we focused on the complex interactions between cardiovascular metabolic alterations and immune responses during the course of CVD. Furthermore, we explore the potential therapeutic interventions that could be developed based on the understanding of metabolic alterations and immune dysregulation in CVD. By targeting these metabolic and immunological pathways, novel strategies for the prevention and treatment of CVDs might be developed to improve patient outcomes and reduce the global burden of this disease.</p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":"175 2","pages":"134-150"},"PeriodicalIF":4.9,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imm.13913","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143700375","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Upregulated TCF1+ Treg Cells With Stronger Function in Systemic Lupus Erythematosus Through Activation of the Wnt-β-Catenin","authors":"Xingyue Zeng, Yiming Gao, Ayibaota Bahabayi, Xiayidan Alimu, Tianci Liu, Mohan Zheng, Zhonghui Zhang, Qi Li, Chen Liu","doi":"10.1111/imm.13914","DOIUrl":"10.1111/imm.13914","url":null,"abstract":"<div>\u0000 \u0000 <p>The role of T-cell factor 1 (TCF1) in human regulatory T cells (Treg) and its clinical significance in systemic lupus erythematosus (SLE) remain unclear. Through bioinformatics analysis and flow cytometry, the <i>Tcf7</i> gene and TCF1 protein were found to be highly expressed in Treg cells. TCF1<sup>+</sup> Treg cells exhibited increased expression of CTLA4 and LAG3 and higher IL-10 secretion than TCF1<sup>−</sup> Treg cells. Circulating TCF1<sup>+</sup> Treg cells were elevated and displayed increased inhibitory markers in SLE patients. The Wnt-β-catenin pathway was activated in TCF1<sup>+</sup> Treg cells in SLE patients. The addition of XAV939 impaired the function of TCF1<sup>+</sup> Treg cells. Clinically, TCF1<sup>+</sup> Treg cells were not only related to CRP, ESR and IL-2, but also could differentiate SLE patients from healthy controls, primary Sjögren's syndrome patients and rheumatoid arthritis patients. In conclusion, the increased TCF1<sup>+</sup> Treg cells in SLE patients indicate a stronger suppressive function for the activated Wnt-β-catenin pathway and help screening and assisting in the diagnosis of SLE patients.</p>\u0000 </div>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":"175 2","pages":"251-262"},"PeriodicalIF":4.9,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143700376","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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