Cellular immunology最新文献

Immunology of familial chorea-acanthocytosis with presenting generalized tonic-clonic seizure: Blood cell study for early diagnosis and management 出现全身强直-阵挛性发作的家族性舞蹈症-棘细胞增多症的免疫学：用于早期诊断和治疗的血细胞研究

IF 3.7 4区医学

Cellular immunology Pub Date : 2025-04-01 DOI: 10.1016/j.cellimm.2025.104946

Amineh Salem, Narges Omidvar

引用次数: 0

Immunity in children: How does it begin?

IF 3.7 4区医学

Cellular immunology Pub Date : 2025-03-24 DOI: 10.1016/j.cellimm.2025.104945

Simon Fillatreau

引用次数: 0

METTL3 promotes infantile pneumonia-induced lung injury by the m6A-TBL1XR1-ACSL1 axis

IF 3.7 4区医学

Cellular immunology Pub Date : 2025-03-16 DOI: 10.1016/j.cellimm.2025.104944

Fuxing Song, Fang Guo, Bo Su, Na Niu, Lina Sun, Min Yan, Min Liu

{"title":"METTL3 promotes infantile pneumonia-induced lung injury by the m6A-TBL1XR1-ACSL1 axis","authors":"Fuxing Song, Fang Guo, Bo Su, Na Niu, Lina Sun, Min Yan, Min Liu","doi":"10.1016/j.cellimm.2025.104944","DOIUrl":"10.1016/j.cellimm.2025.104944","url":null,"abstract":"<div><h3>Background</h3><div>Methyltransferase-like 3 (METTL3) is the catalytic subunit of methyltransferase complex that catalyzes mRNA methylation and has been identified to be involved in lipopolysaccharide (LPS)-induced lung cell injury. In this study, we investigated whether METTL3 is involved in the progression of infantile pneumonia (IP)-induced lung injury and its underlying mechanism.</div></div><div><h3>Methods</h3><div>WI-38 cells were exposed to LPS to induce in vitro proliferation, inflammation, apoptosis, and ferroptosis. The mRNA and protein levels of METTL3, TBL1XR1, IGF2BP1/2/3, and ACSL1 were measured by qRT-PCR and western blotting, respectively. The N6-methyladenosine (m6A) modification was analyzed using a methylated RNA immunoprecipitation assay. Protein interactions were determined using a Co-IP assay. LPS-induced pneumonia in mice was used for the in vivo analysis.</div></div><div><h3>Results</h3><div>METTL3 was highly expressed in IP and LPS-induced WI-38 cells. Knockdown of METTL3 reversed LPS-induced apoptosis, inflammation, and ferroptosis in vitro and in vivo and improved LPS-induced lung injury and collagen deposition in lung tissues of IP mice. Mechanistically, METTL3 induces TBL1XR1 m6A modifications and stabilizes its expression in an m6A-IGF2BP1-dependent manner. Functionally, the protective effects mediated by METTL3 silencing in LPS-treated WI-38 cells were reversed by TBL1XR1 overexpression. In addition, TBL1XR1 interacts with ACSL1, and METTL3 regulates ACSL1 expression via TBL1XR1. Further functional analysis showed that TBL1XR1 deficiency suppressed LPS-induced apoptosis, inflammation, and ferroptosis, which were abolished by ACSL1 up-regulation.</div></div><div><h3>Conclusion</h3><div>METTL3 stabilized TBL1XR1 expression through IGF2BP1-m6A methylation, promoting LPS-induced IP lung injury by upregulating ACSL1 expression.</div></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"411 ","pages":"Article 104944"},"PeriodicalIF":3.7,"publicationDate":"2025-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143673312","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

USP14 inhibits sensitization-mediated degradation of KDM4D to epigenetically regulate dendritic cell tolerogenic capacity and mitigates airway allergy

IF 3.7 4区医学

Cellular immunology Pub Date : 2025-03-13 DOI: 10.1016/j.cellimm.2025.104943

Aizhi Zhang , Huanping Zhang , Le Liu , Hanqing Zhang , Lihua Mo , Wenkai Zhang , Hanis Hazeera Harith , Liying Cheng , Jieping Lv , Chau Ling Tham , Pingchang Yang

{"title":"USP14 inhibits sensitization-mediated degradation of KDM4D to epigenetically regulate dendritic cell tolerogenic capacity and mitigates airway allergy","authors":"Aizhi Zhang , Huanping Zhang , Le Liu , Hanqing Zhang , Lihua Mo , Wenkai Zhang , Hanis Hazeera Harith , Liying Cheng , Jieping Lv , Chau Ling Tham , Pingchang Yang","doi":"10.1016/j.cellimm.2025.104943","DOIUrl":"10.1016/j.cellimm.2025.104943","url":null,"abstract":"<div><div>Numerous immune disorders are caused by the dysfunction of dendritic cells (DC). The mechanism has not been fully comprehended yet. This research is designed to regulate the epigenetic status of lysine-specific demethylase 4D (KDM4D) to enhance DC's immune tolerogenic capacity. In this study, an airway allergy (AA) mouse model was established with dust mite extracts (DME) as the specific antigen. A mouse strain carrying <em>Kdm4d</em>-deficient DCs was employed in the experiments to assess the role of KDM4D in modulating DC's immune tolerogenic functions. The results showed that mice carrying <em>Kdm4d</em>-deficient DCs (KO mice) showed spontaneous Th2 polarization in the airways. Reduced quantities of KDM4D were detected in airway naive DCs (nDCs) of AA mice. The parameters of AA response had a negative correlation with the quantity of KDM4D. The immune tolerogenic capacity of airway nDCs was impaired in KO mice as well as in AA mice. The <em>Il10</em> promoter was found to be hypermethylated in airway nDCs of AA mice and KO mice. The low quantity of deubiquitinating enzyme 14 (USP14) was related to the high level of hyper ubiquitination observed in KDM4D in the <em>Il10</em> promoter locus of airway nDCs of AA mice. Exposure to recombinant USP14 increased the quantity of KDM4D in nDCs, restoring the immune tolerogenic capacity of nDCs in AA mice. In conclusion, dysfunctional tolerogenicity is caused by low levels of KDM4D in airway nDCs from AA mice. USP14 restores the tolerogenic capacity of nDCs in AA mice and mitigates experimental AA.</div></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"411 ","pages":"Article 104943"},"PeriodicalIF":3.7,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143619580","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

Dexmedetomidine modulates peritoneal macrophage to attenuate lipopolysaccharide-induced inflammation

IF 3.7 4区医学

Cellular immunology Pub Date : 2025-03-12 DOI: 10.1016/j.cellimm.2025.104942

Tao Wang , Rui Pan , Jianli Wen , Xinglong Ma

{"title":"Dexmedetomidine modulates peritoneal macrophage to attenuate lipopolysaccharide-induced inflammation","authors":"Tao Wang , Rui Pan , Jianli Wen , Xinglong Ma","doi":"10.1016/j.cellimm.2025.104942","DOIUrl":"10.1016/j.cellimm.2025.104942","url":null,"abstract":"<div><h3>Purpose</h3><div>To investigate how Dexmedetomidine (Dex) modulates the function of peritoneal macrophages (PMs) to reduce lipopolysaccharide (LPS)-induced inflammation.</div></div><div><h3>Methods</h3><div>The anti-inflammatory effect of Dex on LPS-stimulated PMs was assessed by examining its impact on their proliferation, phagocytosis, and polarization. Proliferation and phagocytic activity were measured using CCK-8 and Neutral Red staining assays, respectively. The levels of inflammatory mediators were quantified using ELISA. Additionally, macrophage polarization was evaluated via ELISA, flow cytometry, and Western blot analysis to identify shifts in macrophage phenotypes.</div></div><div><h3>Results</h3><div>Dex increased the proliferation and phagocytic capabilities of PMs, thereby mitigating LPS-induced inflammation. It suppressed pro-inflammatory mediators, including tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and high mobility group box 1 (HMGB1), while increasing levels of the anti-inflammatory cytokine interleukin-10 (IL-10). Furthermore, Dex promoted M2-type macrophage polarization, characterized by increased expression of IL-10, CD206, Arg-1, and CD11c. This effect was mediated through the JAK1/STAT6 signaling pathway, promoting M2 polarization, which was attenuated when JAK1 and STAT6 expression were downregulated.</div></div><div><h3>Conclusion</h3><div>Dex reduces LPS-induced inflammation in part by enhancing the proliferation, phagocytosis, and M2 polarization of PMs, with a key role for the JAK1/STAT6 pathway in promoting anti-inflammatory responses during sepsis.</div></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"411 ","pages":"Article 104942"},"PeriodicalIF":3.7,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143619579","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

Divergent impact of endotoxin priming and endotoxin tolerance on macrophage responses to cancer cells 内毒素引物和内毒素耐受性对巨噬细胞对癌细胞反应的不同影响

IF 3.7 4区医学

Cellular immunology Pub Date : 2025-03-01 DOI: 10.1016/j.cellimm.2025.104934

Konkonika Roy , Tomasz Jędrzejewski , Justyna Sobocińska , Paulina Spisz , Bartosz Maciejewski , Nadine Hövelmeyer , Benedetta Passeri , Sylwia Wrotek

{"title":"Divergent impact of endotoxin priming and endotoxin tolerance on macrophage responses to cancer cells","authors":"Konkonika Roy , Tomasz Jędrzejewski , Justyna Sobocińska , Paulina Spisz , Bartosz Maciejewski , Nadine Hövelmeyer , Benedetta Passeri , Sylwia Wrotek","doi":"10.1016/j.cellimm.2025.104934","DOIUrl":"10.1016/j.cellimm.2025.104934","url":null,"abstract":"<div><div>Endotoxin tolerance (ET) is an adaptive phenomenon that arises from the repeated exposure of immune cells, such as macrophages, to endotoxins like lipopolysaccharide (LPS). Initially, when macrophages are activated by LPS, they produce inflammatory mediators that drive the primary immune response. However, this response is significantly diminished during the establishment of ET, creating an immunosuppressive environment. This environment can facilitate the development and progression of malignant conditions, including cancer.</div><div>Our research focused on the interactions between immune cells and the tumor microenvironment under ET conditions. Through comprehensive <em>in vivo</em> and <em>in vitro</em> studies employing various research techniques, we have demonstrated that interactions between endotoxin-tolerant macrophages (Mo<sub>ET</sub>) and cancer cells contribute to a pro-tumorigenic condition. Notably, we observed that Mo<sub>ET</sub> adapt a pro-tumorigenic, immunosuppressive M2 phenotype (CD163 expression). These macrophages involves distinct metabolic pathways, not depending solely on glycolysis and oxidative phosphorylation. Furthermore, our <em>in vivo</em> findings revealed macrophage infiltration within tumors under both ET and non-ET conditions, highlighting the suppressed immune landscape in the presence of ET. These findings suggest that ET plays a pivotal role in shaping tumor-associated immune responses and that targeting ET pathways could offer a novel and promising therapeutic approach for cancer treatment.</div></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"411 ","pages":"Article 104934"},"PeriodicalIF":3.7,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143561837","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

Seeking tolerance in immunology: Looking back, looking forward

IF 3.7 4区医学

Cellular immunology Pub Date : 2025-03-01 DOI: 10.1016/j.cellimm.2025.104935

David W. Scott

引用次数: 0

Nebulized mesenchymal stem cell-derived exosomes attenuate airway inflammation in a rat model of chronic obstructive pulmonary disease

IF 3.7 4区医学

Cellular immunology Pub Date : 2025-03-01 DOI: 10.1016/j.cellimm.2025.104933

Min Wang , Yuxin Hao , Wei He , Hui Jia , Zhaoshuang Zhong , Shuyue Xia

{"title":"Nebulized mesenchymal stem cell-derived exosomes attenuate airway inflammation in a rat model of chronic obstructive pulmonary disease","authors":"Min Wang , Yuxin Hao , Wei He , Hui Jia , Zhaoshuang Zhong , Shuyue Xia","doi":"10.1016/j.cellimm.2025.104933","DOIUrl":"10.1016/j.cellimm.2025.104933","url":null,"abstract":"<div><div>Chronic Obstructive Pulmonary Disease (COPD) is one of the leading causes of death worldwide, and current treatments fail to significantly halt its progression. Exosomes derived from mesenchymal stem cells (MSCs-Exos) have demonstrated promising potential in treating COPD due to their anti-inflammatory and regenerative biological properties. In this study, we investigated the potential anti-inflammatory effects of bone marrow mesenchymal stem cell-derived exosomes (BMSCs-Exos) in a COPD rat model and the possible mechanisms by which they inhibit airway remodeling, as well as identifying the optimal dosage and administration route. Our results show that nebulized BMSC-Exos significantly improve lung function in COPD rats while reducing pulmonary inflammatory infiltration, bronchial mucus secretion, and collagen deposition. Moreover, BMSC-Exos treatment notably decreased the expression of pro-inflammatory cytokines such as TNF-α, IL-6 and IL-1β, and the pro-fibrotic factor TGF-β1 in serum, bronchoalveolar lavage fluid (BALF), and lung tissue. The most pronounced therapeutic effect was observed at a low dose of exosomes. Furthermore, quantitative real-time PCR and immunohistochemical analyses revealed that nebulized BMSC-Exos significantly inhibited airway remodeling and epithelial–mesenchymal transition (EMT) by suppressing the Wnt/β-catenin signaling pathway. In conclusion, these findings indicate that nebulized BMSC-Exos offer a noninvasive therapeutic strategy for COPD by mitigating lung inflammation and airway remodeling through the suppression of abnormal Wnt/β-catenin pathway activation induced by cigarette smoke (CS) and lipopolysaccharide (LPS) in rats.</div></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"409 ","pages":"Article 104933"},"PeriodicalIF":3.7,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143509101","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

Breast cancer stem cells convert anti-tumor CD4+ T cells to pro-tumor T regulatory cells: Potential role of exosomal FOXP3

IF 3.7 4区医学

Cellular immunology Pub Date : 2025-02-20 DOI: 10.1016/j.cellimm.2025.104931

Udit Basak , Sourio Chakraborty , Sumon Mukherjee , Subhadip Pati , Poulami Khan , Subhajit Ghosh , Arghya Adhikary , Kuladip Jana , Gaurisankar Sa , Tanya Das

{"title":"Breast cancer stem cells convert anti-tumor CD4+ T cells to pro-tumor T regulatory cells: Potential role of exosomal FOXP3","authors":"Udit Basak , Sourio Chakraborty , Sumon Mukherjee , Subhadip Pati , Poulami Khan , Subhajit Ghosh , Arghya Adhikary , Kuladip Jana , Gaurisankar Sa , Tanya Das","doi":"10.1016/j.cellimm.2025.104931","DOIUrl":"10.1016/j.cellimm.2025.104931","url":null,"abstract":"<div><div>Cancer progression and its treatment-response are regulated by the tumor microenvironment (TME). Tumor-initiating cancer stem cells (CSCs) remain in constant communication with the TME, and modulate it through several mechanisms. Here, from <em>in-silico</em> findings and analyzing breast cancer patient tissue-derived data, CSCs and Tregs were found to be positively correlated. Furthermore, our <em>in-silico</em> analyses highlighted a positive relationship between CSC genes and Treg signature marker, FOXP3, even in cancer cell lines that do not contain any T cell or Treg cells, thus raising the possibility of CSCs expressing FOXP3. Validating our hypothesis, higher expression of FOXP3, both at mRNA and protein levels, was observed in breast CSCs than non-stem cancer cells. Since a small population of CSCs initiate tumor in immune cell-dominated TME, we aimed at exploring whether breast CSCs directly transfer FOXP3 to CD4<sup>+</sup>T cells to generate immunosuppressive Treg cells. First, our search revealed CSC-derived exosomes (CDEs) generated CD4<sup>+</sup>CD25<sup>+</sup>FOXP3<sup>+</sup> Tregs at an early time-point of 24 h, which were immunosuppressive in nature. Next, detecting presence of FOXP3 protein in CDEs showed a strong possibility of FOXP3 transfer through CDEs. This was supported by detecting elevated FOXP3 levels from 12 h in translation inhibitor-treated T cells upon CDE-exposure. Finally, exosomes derived from FOXP3 attenuated-CSCs furnished lower FOXP3 in T cells than control CDEs. This mechanism was validated in <em>in-vivo</em> murine model. Together these results indicate a hitherto unexplored role of CSC-derived FOXP3 in reprogramming T cells into immunosuppressive Treg cells.</div></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"409 ","pages":"Article 104931"},"PeriodicalIF":3.7,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143453338","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

In vitro ovarian tumor-conditioned CD163+ human macrophages retain phagocytic response to CD47 blockade

IF 3.7 4区医学

Cellular immunology Pub Date : 2025-02-17 DOI: 10.1016/j.cellimm.2025.104932

Kristian W. Antonsen , Anne G. Jensen , Boe S. Sorensen , Anders Etzerodt , Søren K. Moestrup , Holger J. Møller

{"title":"In vitro ovarian tumor-conditioned CD163+ human macrophages retain phagocytic response to CD47 blockade","authors":"Kristian W. Antonsen , Anne G. Jensen , Boe S. Sorensen , Anders Etzerodt , Søren K. Moestrup , Holger J. Møller","doi":"10.1016/j.cellimm.2025.104932","DOIUrl":"10.1016/j.cellimm.2025.104932","url":null,"abstract":"<div><h3>Introduction</h3><div>CD163-expressing macrophages are abundant in ovarian cancer where they accelerate tumor growth and metastasis. CD47 blockade is a novel immunotherapy aiming to activate macrophage phagocytosis of tumor cells, but it is currently unknown if the tumor-associated macrophages expressing CD163 respond poorly to CD47 blockade.</div></div><div><h3>Methods</h3><div>Human monocyte-derived macrophages were exposed to tumor-conditioned medium from A2780 ovarian cancer cells during differentiation. Effects on gene expression, membrane protein levels, release of soluble proteins and macrophage phagocytosis of A2780 cells in response to CD47 blockade were measured and compared to control macrophages.</div></div><div><h3>Results</h3><div>Tumor cell conditioning induced macrophage expression of CD163 on both the mRNA and protein level. Furthermore, tumor conditioning simultaneously increased protein expression of the phenotype markers CD206 and CD80, and the phagocytosis checkpoint LILRB1. However, tumor conditioning did not reduce phagocytic capacity, as CD47 blockade induced macrophage phagocytosis of A2780 cells to similar degrees in both control and tumor cell-conditioned macrophages.</div></div><div><h3>Discussion</h3><div>In vitro tumor conditioning did not reduce the phagocytic response to CD47 blockade, suggesting that induction of a macrophage phenotype with increased expression of CD163 does not directly limit the capacity for phagocytosis of tumor cells. In conclusion, these findings suggest that CD163+ macrophages remain responsive to CD47 blockade, highlighting their potential as targets for immunotherapy in ovarian cancer.</div></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"409 ","pages":"Article 104932"},"PeriodicalIF":3.7,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143464189","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0