{"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}
{"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}
{"title":"Yersinia pestis and pneumonic plague: Insight into how a lethal pathogen interfaces with innate immune populations in the lung to cause severe disease","authors":"Gopinath Venugopal, Roger D. Pechous","doi":"10.1016/j.cellimm.2024.104856","DOIUrl":"10.1016/j.cellimm.2024.104856","url":null,"abstract":"<div><p><em>Yersinia pestis</em> is the causative agent of bubonic, septicemic and pneumonic plague. The historical importance and potential of plague to re-emerge as a threat worldwide are indisputable. The most severe manifestion of plague is pneumonic plague, which results in disease that is 100% lethal without treatment. <em>Y. pestis</em> suppresses host immune responses early in the lung to establish infection. The later stages of infection see the rapid onset of hyperinflammatory responses that prove lethal. The study of <em>Y. pestis</em> host/pathogen interactions have largely been investigated during bubonic plague and with attenuated strains in cell culture models. There remains a somewhat limited understanding of the interactions between virulent <em>Y. pestis</em> and immune populations in the lung that drive severe disease. In this review we give a broad overview of the progression of pneumonic plague and highlighting how <em>Y. pestis</em> interfaces with host innate immune populations in the lung to cause lethal disease.</p></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141603373","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":"Tumor micro-environment induced TRAIL secretion from engineered macrophages for anti-tumor therapy","authors":"","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":null,"pages":null},"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}
{"title":"Additional use of α-IgM antibodies potentiates CpG ODN2006-induced B cell activation by targeting mainly naïve and marginal zone-like B cells","authors":"Leonie Fleige , Simon Fillatreau , Maren Claus , Silvia Capellino","doi":"10.1016/j.cellimm.2024.104846","DOIUrl":"https://doi.org/10.1016/j.cellimm.2024.104846","url":null,"abstract":"<div><p>CpG ODN2006 is widely used as a potent B cell stimulant <em>in vitro</em> and <em>in vivo</em>. However, it shows a deficit in targeting naïve B cells <em>in vitro</em>. In this study, we investigated whether α-IgM can support ODN2006-induced effects on B cells to obtain enhanced activation with focus on different B cell subsets.</p><p>Our results delineated robust B cell activation, shown by increased activation marker expression and cytokine secretion by each agent alone, and further augmented when used in combination. Interestingly, α-IgM targeted mainly naïve and marginal zone-like B cells, thus complementing the pronounced effects of ODN2006 on memory B cells and achieving optimal activation for all B cell subsets.</p><p>Taken together, combining ODN2006 and α-IgM is beneficial for <em>in vitro</em> activation including all B cell subsets. Furthermore, our results suggest that α-IgM could enhance efficacy of ODN2006 <em>in vivo</em> with further need of investigation.</p></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141594084","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}
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":null,"pages":null},"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}
{"title":"Peyer’s Patch: Possible target for modulating the Gut-Brain-Axis through microbiota","authors":"Reza Asgari , Mohammad Amin Bazzazan , Ashkan Karimi Jirandehi , Salar Yousefzadeh , Masood Alaei , Sanaz Keshavarz Shahbaz","doi":"10.1016/j.cellimm.2024.104844","DOIUrl":"https://doi.org/10.1016/j.cellimm.2024.104844","url":null,"abstract":"<div><p>The gastrointestinal (GI) tract and the brain form bidirectional nervous, immune, and endocrine communications known as the gut-brain axis. Several factors can affect this axis; among them, various studies have focused on the microbiota and imply that alterations in microbiota combinations can influence both the brain and GI. Also, many studies have shown that the immune system has a vital role in varying gut microbiota combinations. In the current paper, we will review the multidirectional effects of gut microbiota, immune system, and nervous system on each other. Specifically, this review mainly focuses on the impact of Peyer’s patches as a critical component of the gut immune system on the gut-brain axis through affecting the gut’s microbial composition. In this way, some factors were discussed as proposed elements of missing gaps in this field.</p></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2024-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141428778","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}
Chandreyee Datta , Pradip Das , Surbhi Swaroop, Ashish Bhattacharjee
{"title":"Rac1 plays a crucial role in MCP-1-induced monocyte adhesion and migration","authors":"Chandreyee Datta , Pradip Das , Surbhi Swaroop, Ashish Bhattacharjee","doi":"10.1016/j.cellimm.2024.104843","DOIUrl":"https://doi.org/10.1016/j.cellimm.2024.104843","url":null,"abstract":"<div><p>Monocyte migration is an important process in inflammation and atherogenesis. Identification of the key signalling pathways that regulate monocyte migration can provide prospective targets for prophylactic treatments in inflammatory diseases. Previous research showed that the focal adhesion kinase Pyk2, Src kinase and MAP kinases play an important role in MCP-1-induced monocyte migration. In this study, we demonstrate that MCP-1 induces iPLA<sub>2</sub> activity, which is regulated by PKCβ and affects downstream activation of Rac1 and Pyk2. Rac1 interacts directly with iPLA<sub>2</sub> and Pyk2, and plays a crucial role in MCP-1-mediated monocyte migration by modulating downstream Pyk2 and p38 MAPK activation. Furthermore, Rac1 is necessary for cell spreading and F-actin polymerization during monocyte adhesion to fibronectin. Finally, we provide evidence that Rac1 controls the secretion of inflammatory mediator vimentin from MCP-1-stimulated monocytes. Altogether, this study demonstrates that the PKCβ/iPLA<sub>2</sub>/Rac1/Pyk2/p38 MAPK signalling cascade is essential for MCP-1-induced monocyte adhesion and migration.</p></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141434313","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}
Danqi Sun , Kai Wang , Youmou Chen , Beiying Zhang , Jun Tang , Wei Luo , Jia Liu , Sifei Yu
{"title":"Immunological characteristics of CD103+CD161+ T lymphocytes on chronic rhinosinusitis with nasal polyps","authors":"Danqi Sun , Kai Wang , Youmou Chen , Beiying Zhang , Jun Tang , Wei Luo , Jia Liu , Sifei Yu","doi":"10.1016/j.cellimm.2024.104842","DOIUrl":"10.1016/j.cellimm.2024.104842","url":null,"abstract":"<div><p>Chronic rhinosinusitis with nasal polyps (CRSwNPs) is a heterogeneous disease characterized by local inflammation of the upper airway and sinus mucosa. T cell-mediated immune responses play irreplaceable roles in the pathogenesis of nasal polyps. CD161<sup>+</sup> T cells have been implicated in the pathology of several diseases through cytokine production and cytotoxic activity. However, the immunological characteristics of CD161<sup>+</sup> T cells in nasal mucosa are still not well understood, particularly in CRSwNPs. Our research revealed a notable enrichment of CD161<sup>+</sup> T cells in nasal tissues compared to peripheral blood, with a significantly more infiltration of CD161<sup>+</sup> T cells in CRSwNPs compared to control nasal samples. Phenotypical analysis found that CD161<sup>+</sup> T cells predominantly co-expressed tissue-resident memory surface markers CD103, CD69, and CD45RO. CD161<sup>+</sup>CD103<sup>+</sup> T cells demonstrated complicated effector functions, marked by elevated levels of PD-1, CTLA-4, IL-17, and IFN-γ and diminished expression of FoxP3 and CD25. Interestingly, despite CD161<sup>+</sup> T cells was more abundant in polyp tissues compared to normal control tissues, and then further categorizing polyp samples into distinct groups based on clinical characteristics, only the recurrent CRSwNP group showed a significant reduction in CD161<sup>+</sup>CD8<sup>+</sup> T cells compared to the primary CRSwNP group. This finding suggested the necessity for further research to comprehensively understand the underlying mechanisms and the broader significance of CD161<sup>+</sup> T cells in the advancement and relapse of CRSwNPs.</p></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2024-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141409576","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":"Extra-pulmonary control of respiratory defense","authors":"Filiz T. Korkmaz, Lee J. Quinton","doi":"10.1016/j.cellimm.2024.104841","DOIUrl":"https://doi.org/10.1016/j.cellimm.2024.104841","url":null,"abstract":"<div><p>Pneumonia persists as a public health crisis, representing the leading cause of death due to infection. Whether respiratory tract infections progress to pneumonia and its sequelae such as acute respiratory distress syndrome and sepsis depends on numerous underlying conditions related to both the causative agent and host. Regarding the former, pneumonia burden remains staggeringly high, despite the effectiveness of pathogen-targeting strategies such as vaccines and antibiotics. This demands a greater understanding of host features that collaborate to promote immune resistance and tissue resilience in the infected lung. Such features inside the pulmonary compartment have drawn much attention, where major advances have been made related to resident and recruited immune activity. By comparison, extra-pulmonary processes guiding pneumonia susceptibility are relatively elusive, constituting the focus of this review. Here we will highlight examples of when, how, and why tissues outside of the lungs dispatch signals that modulate local immunity in the airspaces. Topics include the liver, gut, bone marrow, brain and more, all of which contribute in direct and indirect ways to pneumonia outcome. When tuned appropriately, it has become clear that these responses can serve protective roles, and this will be considered distinctly from what would otherwise be aberrant responses characteristic of pneumonia-induced organ injury and sepsis. Further advances in this area may reveal novel targetable areas for clinical intervention that are not confined to the intra-pulmonary space.</p></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2024-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141324034","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}