Cellular immunology最新文献

Glutathione regulates CIA-activated splenic-lymphocytes via NF-κB/MMP-9 and MAPK/PCNA pathways manipulating immune response 谷胱甘肽通过 NF-κB/MMP-9 和 MAPK/PCNA 通路调节 CIA 激活的脾淋巴细胞，从而操纵免疫反应

IF 3.7 4区医学

Cellular immunology Pub Date : 2024-09-03 DOI: 10.1016/j.cellimm.2024.104866

{"title":"Glutathione regulates CIA-activated splenic-lymphocytes via NF-κB/MMP-9 and MAPK/PCNA pathways manipulating immune response","authors":"","doi":"10.1016/j.cellimm.2024.104866","DOIUrl":"10.1016/j.cellimm.2024.104866","url":null,"abstract":"<div><p>Reduced glutathione (GSH) is an antioxidant involved in redox homeostasis, and recently regarded as an inducer of Reductive stress. Its immune-regulatory effects on lymphocytes have not been extensively studied. This study is based on the finding that much increased GSH level in collagen-induced arthritis (CIA) rat spleen, and aimed to investigate the effects of GSH (0, 1, 10, 100 mM) on normal and immune-stimulated spleen lymphocytes respectively. The elevated GSH level is associated with the increased levels of inflammatory factors; especially the increased DPP1 activity indicated immune-granulocytes activation in CIA rat spleen. Exogenous GSH had different influences on normal and CIA lymphocytes, affecting intracellular levels of GSH, Glutathione-S-transferases (GSTs) and Reactive oxygen species (ROS); as well as the expressions of NF-κB, MMP-9, Bcl-2, GST, P38, PCNA and TLR4. The increased extracellular GSH level disturbed redox homeostasis and induces reductive stress to spleen lymphocytes, which decreased intracellular GSH concentration and influenced the MAPK/PCNA and NF-κB/MMP-9 signaling pathways, as well as cell cycles respectively, leading to cell senescence/ferroptosis/apoptosis. This study also revealed the multiple faces of GSH in regulating spleen lymphocytes, which depended on its levels in tissue or in cells, and the activation status of lymphocytes. These findings indicate the immune-regulatory role of GSH on spleen-lymphocytes, and the high level GSH in CIA rat spleens may contribute to CIA development.</p></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142157502","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

BCG immunization induced KLRG1+ NK cells show memory-like responses to mycobacterial and HIV antigens 卡介苗免疫诱导的 KLRG1+ NK 细胞对分枝杆菌和艾滋病毒抗原表现出类似记忆的反应

IF 3.7 4区医学

Cellular immunology Pub Date : 2024-09-01 DOI: 10.1016/j.cellimm.2024.104865

引用次数: 0

The role of mitochondrial fusion and fission in immune-mediated inflammatory diseases 线粒体融合与分裂在免疫介导的炎症性疾病中的作用

IF 3.7 4区医学

Cellular immunology Pub Date : 2024-08-26 DOI: 10.1016/j.cellimm.2024.104864

引用次数: 0

Cbl-b inhibition promotes less differentiated phenotypes of T cells with enhanced cytokine production 抑制 Cbl-b 可促进分化程度较低的 T 细胞表型，并增强细胞因子的产生

IF 3.7 4区医学

Cellular immunology Pub Date : 2024-08-23 DOI: 10.1016/j.cellimm.2024.104863

{"title":"Cbl-b inhibition promotes less differentiated phenotypes of T cells with enhanced cytokine production","authors":"","doi":"10.1016/j.cellimm.2024.104863","DOIUrl":"10.1016/j.cellimm.2024.104863","url":null,"abstract":"<div><p>For adoptive therapy with T cell receptor engineered T (TCR-T) cells, the quantity and quality of the final cell product directly affect their anti-tumor efficacy. The post-transfer efficacy window of TCR-T cells is keen to optimizing attempts during the manufacturing process. Cbl-b is a E3 ubiquitin ligase previously shown with critical negative impact in T cell functions. This study investigated whether strategic inclusion of a commercially available small inhibitor targeting Cbl-b (Cbl-<em>b</em>-IN-1) prior to T cell activation could enhance the quality of the final TCR-T cell product. Examination with both PBMCs and TCR-T cells revealed that Cbl-<em>b</em>-IN-1 treatment promoted TCR expression efficiency, T cell proliferation potential and, specifically, cell survival capability post antigenic stimulation. Cbl-<em>b</em>-IN-1 exposure facilitated T cells in maintaining less differentiated states with enhanced cytokine production. Further, we found that Cbl-<em>b</em>-IN-1 effectively augmented the activation of TCR signaling, shown by increased phosphorylation levels of Zeta-chain-associated protein kinase 70 (ZAP70) and phospholipase c-γ1 (PLCγ1). In conclusion, our results evidence that the inclusion of Cbl-b inhibitor immediately prior to TCR-T cell activation may enhance their proliferation, survival, and function potentials, presenting an applicable optimization strategy for immunotherapy with adoptive cell transfer.</p></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142058390","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

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

{"title":"RORα negatively regulates BCG-induced trained immunity","authors":"","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":null,"pages":null},"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

{"title":"HIF-1α is required to differentiate the neonatal Macrophage protein secretome from adults","authors":"","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":null,"pages":null},"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

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

{"title":"ZFP36 family expression is suppressed by Th2 cells in asthma, leading to enhanced synthesis of inflammatory cytokines and cell surface molecules","authors":"","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":null,"pages":null},"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

{"title":"Petunidin suppresses Hashimoto’s thyroiditis by regulating Th1/Th17 homeostasis and oxidative stress","authors":"","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":null,"pages":null},"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