Cellular immunology最新文献_第3页

RORα negatively regulates BCG-induced trained immunity RORα 负向调节卡介苗诱导的训练有素的免疫力

IF 3.7 4区医学

Cellular immunology Pub Date : 2024-08-15 DOI: 10.1016/j.cellimm.2024.104862

Gizem Kilic , Vasiliki Matzaraki , Ozlem Bulut , Ilayda Baydemir , Anaisa V. Ferreira , Katrin Rabold , Simone J.C.F.M. Moorlag , Valerie A.C.M. Koeken , L. Charlotte J. de Bree , Vera P. Mourits , Leo A.B. Joosten , Jorge Domínguez-Andrés , Mihai G. Netea

{"title":"RORα negatively regulates BCG-induced trained immunity","authors":"Gizem Kilic , Vasiliki Matzaraki , Ozlem Bulut , Ilayda Baydemir , Anaisa V. Ferreira , Katrin Rabold , Simone J.C.F.M. Moorlag , Valerie A.C.M. Koeken , L. Charlotte J. de Bree , Vera P. Mourits , Leo A.B. Joosten , Jorge Domínguez-Andrés , Mihai G. Netea","doi":"10.1016/j.cellimm.2024.104862","DOIUrl":"10.1016/j.cellimm.2024.104862","url":null,"abstract":"<div><p>Trained immunity is a long-lasting change in the responsiveness of innate immune cells, leading to a stronger response upon an unrelated secondary challenge. Epigenetic, transcriptional, and metabolic reprogramming contribute to the development of trained immunity. By investigating the impact of gene variants on trained immunity responses after Bacillus Calmette–Guérin (BCG) vaccination, we identified a strong association between polymorphisms in the <em>RORA</em> gene and BCG-induced trained immunity in PBMCs isolated from healthy human donors. RORα, encoded by the <em>RORA</em> gene in humans, is a nuclear receptor and a transcription factor, regulating genes involved in circadian rhythm, inflammation, cholesterol, and lipid metabolism. We found that natural RORα agonists in the circulation negatively correlate with the strength of trained immunity responses after BCG vaccination. Moreover, pharmacological inhibition of RORα in human PBMCs led to higher cytokine production capacity and boosted trained immunity induction by BCG. Blocking RORα activity also resulted in morphological changes and increased ROS and lactate production of BCG-trained cells. Blocking lactate dehydrogenase A (LDHA) and glycolysis with sodium oxamate reduced the cytokine production capacity of cells trained with a combination of BCG and the RORα agonist. In conclusion, this study highlights the potential role of RORα in trained immunity, and its impact on human vaccination and diseases should be further investigated.</p></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"403 ","pages":"Article 104862"},"PeriodicalIF":3.7,"publicationDate":"2024-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0008874924000650/pdfft?md5=583ca87c5448531dfd921a10c233d07d&pid=1-s2.0-S0008874924000650-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142002445","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

HIF-1α is required to differentiate the neonatal Macrophage protein secretome from adults HIF-1α是将新生儿巨噬细胞蛋白分泌组与成人巨噬细胞蛋白分泌组进行分化所必需的。

IF 3.7 4区医学

Cellular immunology Pub Date : 2024-08-02 DOI: 10.1016/j.cellimm.2024.104861

Amanda Becker , Mallory Filipp , Connor Lantz , Kristofor Glinton , Edward B. Thorp

{"title":"HIF-1α is required to differentiate the neonatal Macrophage protein secretome from adults","authors":"Amanda Becker , Mallory Filipp , Connor Lantz , Kristofor Glinton , Edward B. Thorp","doi":"10.1016/j.cellimm.2024.104861","DOIUrl":"10.1016/j.cellimm.2024.104861","url":null,"abstract":"<div><p>The immune response to stress diverges with age, with neonatal macrophages implicated in tissue regeneration versus tissue scarring and maladaptive inflammation in adults. Integral to the macrophage stress response is the recognition of hypoxia and pathogen-associated molecular patterns (PAMPs), which are often coupled. The age-specific, cell-intrinsic nature of this stress response remains vague. To uncover age-defined divergences in macrophage crosstalk potential after exposure to hypoxia and PAMPs, we interrogated the secreted proteomes of neonatal versus adult macrophages via non-biased mass spectrometry. Through this approach, we newly identified age-specific signatures in the secretomes of neonatal versus adult macrophages in response to hypoxia and the prototypical PAMP, lipopolysaccharide (LPS). Neonatal macrophages secreted proteins most consistent with an anti-inflammatory, regenerative phenotype protective against apoptosis and oxidative stress, dependent on <em>hypoxia inducible transcription factor-1α</em> (<em>HIF-1α).</em> In contrast, adult macrophages secreted proteins consistent with a pro-inflammatory, glycolytic phenotypic signature consistent with pathogen killing. Taken together, these data uncover fundamental age and <em>HIF-1α</em> dependent macrophage responses that may be targeted to calibrate the innate immune response during stress and inflammation.</p></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"403 ","pages":"Article 104861"},"PeriodicalIF":3.7,"publicationDate":"2024-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141888576","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

R406 reduces lipopolysaccharide-induced neutrophil activation R406 可减少脂多糖诱导的中性粒细胞活化

IF 3.7 4区医学

Cellular immunology Pub Date : 2024-07-26 DOI: 10.1016/j.cellimm.2024.104860

Seth Warner , Heather L. Teague , Marcos J. Ramos-Benitez , Sumith Panicker , Kiana Allen , Salina Gairhe , Tom Moyer , Bindu Parachalil Gopalan , Iyadh Douagi , Arun Shet , Yogendra Kanthi , Anthony F. Suffredini , Daniel S. Chertow , Jeffrey R. Strich

{"title":"R406 reduces lipopolysaccharide-induced neutrophil activation","authors":"Seth Warner , Heather L. Teague , Marcos J. Ramos-Benitez , Sumith Panicker , Kiana Allen , Salina Gairhe , Tom Moyer , Bindu Parachalil Gopalan , Iyadh Douagi , Arun Shet , Yogendra Kanthi , Anthony F. Suffredini , Daniel S. Chertow , Jeffrey R. Strich","doi":"10.1016/j.cellimm.2024.104860","DOIUrl":"10.1016/j.cellimm.2024.104860","url":null,"abstract":"<div><p>Modulating SYK has been demonstrated to have impacts on pathogenic neutrophil responses in COVID-19. During sepsis, neutrophils are vital in early bacterial clearance but also contribute to the dysregulated immune response and organ injury when hyperactivated. Here, we evaluated the impact of R406, the active metabolite of fostamatinib, on neutrophils stimulated by LPS. We demonstrate that R406 was able to effectively inhibit NETosis, degranulation, ROS generation, neutrophil adhesion, and the formation of CD16<sup>low</sup> neutrophils that have been linked to detrimental outcomes in severe sepsis. Further, the neutrophils remain metabolically active, capable of releasing cytokines, perform phagocytosis, and migrate in response to IL-8. Taken together, this data provides evidence of the potential efficacy of utilizing fostamatinib in bacterial sepsis.</p></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"403 ","pages":"Article 104860"},"PeriodicalIF":3.7,"publicationDate":"2024-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0008874924000637/pdfft?md5=e8b6e53a2f70a588ccaf008ab84bc642&pid=1-s2.0-S0008874924000637-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141846121","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

ZFP36 family expression is suppressed by Th2 cells in asthma, leading to enhanced synthesis of inflammatory cytokines and cell surface molecules ZFP36 家族的表达受到哮喘 Th2 细胞的抑制，导致炎症细胞因子和细胞表面分子的合成增强。

IF 3.7 4区医学

Cellular immunology Pub Date : 2024-07-23 DOI: 10.1016/j.cellimm.2024.104859

Yuki Uehara , Maho Suzukawa , Masafumi Horie , Sayaka Igarashi , Masaaki Minegishi , Kazufumi Takada , Akira Saito , Hiroyuki Nagase

{"title":"ZFP36 family expression is suppressed by Th2 cells in asthma, leading to enhanced synthesis of inflammatory cytokines and cell surface molecules","authors":"Yuki Uehara , Maho Suzukawa , Masafumi Horie , Sayaka Igarashi , Masaaki Minegishi , Kazufumi Takada , Akira Saito , Hiroyuki Nagase","doi":"10.1016/j.cellimm.2024.104859","DOIUrl":"10.1016/j.cellimm.2024.104859","url":null,"abstract":"<div><p>Asthma is a chronic inflammatory airway disease, in which inflammatory cytokines play a pivotal role. The zinc finger binding protein 36 (ZFP36) family includes ZFP36, ZFP36L1, and ZFP36L2 and is among the RNA-binding proteins (RBPs) reported to cause inflammation. The present study aimed to clarify the roles of the ZFP36 family in asthma, particularly highlighting the relationship between the ZFP36 family and Th2 cells, which are key players in type 2 inflammation in asthma. Real-time PCR analysis revealed the preferential expression of <em>ZFP36</em> family mRNAs in human white blood cells. Gene expression analysis using public datasets from the GEO database (<span><span>https://www.ncbi.nlm.nih.gov/gds</span><svg><path></path></svg></span>) showed significantly suppressed expression of <em>ZFP36</em> family mRNAs in patients with asthma compared to that in healthy controls. Using multiple cytokine assays, Th2 cell transfection with <em>ZFP36</em> family siRNAs enhanced the expression of inflammatory cytokines IL-8, IFN-γ, CCL3/MIP-1α, CCL4/MIP-1β, and TNF-α and cell surface molecules CCR4 (CD194) and PSGL-1 (CD162). Treatment with IL-2, 4, and 15 significantly suppressed, and corticosteroid significantly enhanced the expressions of <em>ZFP36</em> family mRNAs by Th2 cells. In conclusion, the ZFP36 family expressed by Th2 cells was suppressed in patients with asthma, leading to the enhanced expression of cytokines and cell surface molecules. Suppressed ZFP36 expression in asthma may be involved in the enhancement of airway inflammation, and the ZFP36 family may be a therapeutic target for inflammatory diseases, including asthma.</p></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"403 ","pages":"Article 104859"},"PeriodicalIF":3.7,"publicationDate":"2024-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141787283","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

Petunidin suppresses Hashimoto’s thyroiditis by regulating Th1/Th17 homeostasis and oxidative stress 矮牵牛素通过调节Th1/Th17平衡和氧化应激抑制桥本氏甲状腺炎

IF 3.7 4区医学

Cellular immunology Pub Date : 2024-07-17 DOI: 10.1016/j.cellimm.2024.104858

Beiyan Liu , Lin Li , Xu Wang

{"title":"Petunidin suppresses Hashimoto’s thyroiditis by regulating Th1/Th17 homeostasis and oxidative stress","authors":"Beiyan Liu , Lin Li , Xu Wang","doi":"10.1016/j.cellimm.2024.104858","DOIUrl":"10.1016/j.cellimm.2024.104858","url":null,"abstract":"<div><p>Hashimoto’s thyroiditis (HT) is a prevalent autoimmune thyroid disease, necessitating further research to identify effective treatment strategies. Two key pathophysiological factors of HT are inflammation and oxidative stress. Petunidin (PET) is an anthocyanin with anti-inflammatory and antioxidant properties. This study aimed to investigate the effect and mechanism of PET on HT. C57BL/6N mice were injected with thyroglobulin emulsified with adjuvant to establish the HT animal model. Our results showed that PET administration decreased the concentrations of TPOAb, TgAb, T3, T4, IgG, IgA and IgM in HT mice, accompanied by significant alterations in follicle shape and increased lymphocyte infiltrations. Additionally, the apoptosis rate, ROS level, MDA content, CD4+ level, IFN-γ and IL-17A levels, as well as the concentrations of IFN-γ and IL-17, were elevated in HT mice and reduced by PET treatment. Furthermore, HT patients exhibited higher levels of NOX4 and PKM2, which were positively correlated with TPOAb, IFN-γ, and IL-17 concentrations. In HT mice, PET therapy decreased the expression of PKM2 and NOX4 proteins. In summary, PET can improve thyroid dysfunction by suppressing apoptosis, oxidative stress and Th1/Th17 differentiation through regulation of the NOX4/PKM2 axis in HT mice, suggesting its promising potential for HT intervention.</p></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"403 ","pages":"Article 104858"},"PeriodicalIF":3.7,"publicationDate":"2024-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141757381","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

Yersinia pestis and pneumonic plague: Insight into how a lethal pathogen interfaces with innate immune populations in the lung to cause severe disease 鼠疫耶尔森菌和肺鼠疫：洞察致命病原体如何与肺部先天性免疫种群相互作用，从而导致严重疾病。

IF 3.7 4区医学

Cellular immunology Pub Date : 2024-07-10 DOI: 10.1016/j.cellimm.2024.104856

Gopinath Venugopal, Roger D. Pechous

引用次数: 0

Tumor micro-environment induced TRAIL secretion from engineered macrophages for anti-tumor therapy 肿瘤微环境诱导工程巨噬细胞分泌 TRAIL，用于抗肿瘤治疗

IF 3.7 4区医学

Cellular immunology Pub Date : 2024-07-10 DOI: 10.1016/j.cellimm.2024.104857

Qinyao Zhu , Xin Huang , Botian Deng , Lili Guan , Hui Zhou , Binhe Shi , Junhua Liu , Xiaojiao Shan , Xiaobin Fang , Fengtao Xu , Huan Li , Xiyang Liu , Xiushan Yin , Luo Zhang

{"title":"Tumor micro-environment induced TRAIL secretion from engineered macrophages for anti-tumor therapy","authors":"Qinyao Zhu , Xin Huang , Botian Deng , Lili Guan , Hui Zhou , Binhe Shi , Junhua Liu , Xiaojiao Shan , Xiaobin Fang , Fengtao Xu , Huan Li , Xiyang Liu , Xiushan Yin , Luo Zhang","doi":"10.1016/j.cellimm.2024.104857","DOIUrl":"10.1016/j.cellimm.2024.104857","url":null,"abstract":"<div><p>The high plasticity and long-term persistency make macrophages excellent vehicles for delivering anti-tumor cytokines. Macrophage delivery of chemokines and cytokines shows potential in tumor therapy. TRAIL, a promising anti-tumor cytokine, induces apoptosis in tumor cells with low toxicity to normal cells. However, its off-target toxicity and limited stability have limited its clinical progress. Here, we engineered macrophages with Mono-TRAIL and Tri-TRAIL and found that Tri-TRAIL had higher cytotoxic activity against tumor cells than Mono-TRAIL in vitro. To target the tumor microenvironment (TME), we generated macrophages secreting trimeric TRAIL (Tri-TRAIL-iM) induced by the TME-specific promoter Arg1. The Tri-TRAIL-iM cells displayed high specific activatable activity in cell-based co-culture assay and tumor-baring mice models. In addition, we demonstrated that compared to macrophages over-expressing TRAIL under a non-inducible promoter, Tri-TRAIL-iM could more effectively induce apoptosis in cancer cells, inhibit tumor growth, and reduce systemic side effects. This strategy of inducing TRAIL delivery holds great potential for cancer therapy. It is promising to be combined with other engineering methods to maximize the therapeutic effects of solid tumors.</p></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"403 ","pages":"Article 104857"},"PeriodicalIF":3.7,"publicationDate":"2024-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141691827","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

Additional use of α-IgM antibodies potentiates CpG ODN2006-induced B cell activation by targeting mainly naïve and marginal zone-like B cells 额外使用 α-IgM 抗体可通过主要靶向幼稚和边缘区样 B 细胞，增强 CpG ODN2006 诱导的 B 细胞活化作用

IF 3.7 4区医学

Cellular immunology Pub Date : 2024-07-06 DOI: 10.1016/j.cellimm.2024.104846

Leonie Fleige , Simon Fillatreau , Maren Claus , Silvia Capellino

引用次数: 0

CD147 regulates the formation and function of immune synapses CD147 可调节免疫突触的形成和功能。

IF 3.7 4区医学

Cellular immunology Pub Date : 2024-06-19 DOI: 10.1016/j.cellimm.2024.104845

Yingming Xu , Kui Zhang , Jinlin Miao , Na Guo , Xianghui Fu , Fengfan Yang , Xing Luo , Junfeng Jia , Zhaohui Zheng , Ping Zhu

{"title":"CD147 regulates the formation and function of immune synapses","authors":"Yingming Xu , Kui Zhang , Jinlin Miao , Na Guo , Xianghui Fu , Fengfan Yang , Xing Luo , Junfeng Jia , Zhaohui Zheng , Ping Zhu","doi":"10.1016/j.cellimm.2024.104845","DOIUrl":"10.1016/j.cellimm.2024.104845","url":null,"abstract":"<div><p>CD147 is a T cell activation-associated molecule which is closely involved in the formation of the immune synapse (IS). However, the precise role of CD147 in T cell activation and IS formation remains unclear. In the present study, we demonstrated that CD147 translocated to the IS upon T cell activation and was primarily distributed in the peripheral super molecular cluster (p-SMAC). The knock down of CD147 expression in T cells, but not in B cells, impaired IS formation. CD147 participated in IS formation between T cells and different types of antigen-presenting cells (APCs), including macrophages and dendritic cells. Ligation of CD147 with its monoclonal antibody (mAb) HAb18 effectively inhibited T cell activation and IL-2 secretion. CD98, a critical molecule interacting with CD147, was distributed in IS in a CD147-dependent way. Phosphorylation levels of T cell receptor (TCR) related molecules, like ZAP-70, ERK, and cJun, were down-regulated by CD147 ligation, which is crucial for the interaction of CD147 and TCR signaling transduction. CD147 is indispensable for the formation of immune synapses and plays an important role in the regulation of its function.</p></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"401 ","pages":"Article 104845"},"PeriodicalIF":3.7,"publicationDate":"2024-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0008874924000480/pdfft?md5=a7f39d5adf08f4e860ff8692af8f6d1e&pid=1-s2.0-S0008874924000480-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141442111","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

Peyer’s Patch: Possible target for modulating the Gut-Brain-Axis through microbiota 佩尔氏斑：通过微生物群调节肠-脑-轴的可能目标

IF 4.3 4区医学

Cellular immunology Pub Date : 2024-06-18 DOI: 10.1016/j.cellimm.2024.104844

Reza Asgari , Mohammad Amin Bazzazan , Ashkan Karimi Jirandehi , Salar Yousefzadeh , Masood Alaei , Sanaz Keshavarz Shahbaz

引用次数: 0