Cellular immunology最新文献_第6页

The research progression of direct NLRP3 inhibitors to treat inflammatory disorders 直接 NLRP3 抑制剂治疗炎症性疾病的研究进展

IF 4.3 4区医学

Cellular immunology Pub Date : 2024-01-24 DOI: 10.1016/j.cellimm.2024.104810

Xiu Chen, Pingping Zhang, Yu Zhang, Mengzhu Wei, Tian Tian, Dacheng Zhu, Yanling Guan, Wei Wei, Yang Ma

{"title":"The research progression of direct NLRP3 inhibitors to treat inflammatory disorders","authors":"Xiu Chen, Pingping Zhang, Yu Zhang, Mengzhu Wei, Tian Tian, Dacheng Zhu, Yanling Guan, Wei Wei, Yang Ma","doi":"10.1016/j.cellimm.2024.104810","DOIUrl":"10.1016/j.cellimm.2024.104810","url":null,"abstract":"<div><p>The NLRP3 inflammasome represents a cytoplasmic multiprotein complex with the capability to recognize a wide range of pathogen-derived, environmental, and endogenous stress-related factors. Dysregulated activation of the NLRP3 inflammasome has been implicated in the development of various inflammasome-associated disorders, highlighting its significance as a pivotal target for the treatment of inflammatory diseases. Nonetheless, despite its clinical importance, there is currently a lack of specific drugs available for directly targeting the NLRP3 inflammasome. Several strategies have been explored to target different facets of the NLRP3 inflammasome, with interventions aimed at directly inhibiting NLRP3 demonstrating the most promising efficacy and safety profiles. In this review, we provide a summary of direct inhibitors targeting NLRP3, elucidating their inhibitory mechanisms, clinical trial phases, and potential applications. Through this discussion, we aim to shed light on the implications of NLRP3 inhibition for the treatment of inflammatory diseases.</p></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"397 ","pages":"Article 104810"},"PeriodicalIF":4.3,"publicationDate":"2024-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139556090","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

The mechanism by which cannabidiol (CBD) suppresses TNF-α secretion involves inappropriate localization of TNF-α converting enzyme (TACE) 大麻二酚（CBD）抑制 TNF-α 分泌的机制涉及 TNF-α 转换酶（TACE）的不当定位

IF 4.3 4区医学

Cellular immunology Pub Date : 2024-01-17 DOI: 10.1016/j.cellimm.2024.104812

Christa M. Frodella , Liyuan Liu , Wei Tan , Stephen B. Pruett , Barbara L.F. Kaplan

{"title":"The mechanism by which cannabidiol (CBD) suppresses TNF-α secretion involves inappropriate localization of TNF-α converting enzyme (TACE)","authors":"Christa M. Frodella , Liyuan Liu , Wei Tan , Stephen B. Pruett , Barbara L.F. Kaplan","doi":"10.1016/j.cellimm.2024.104812","DOIUrl":"10.1016/j.cellimm.2024.104812","url":null,"abstract":"<div><p>Cannabidiol (CBD) is a phytocannabinoid derived from <em>Cannabis sativa</em> that exerts anti-inflammatory mechanisms. CBD is being examined for its putative effects on the neuroinflammatory disease, multiple sclerosis (MS). One of the major immune mediators that propagates MS and its mouse model experimental autoimmune encephalomyelitis (EAE) are macrophages. Macrophages can polarize into an inflammatory phenotype (M1) or an anti-inflammatory phenotype (M2a). Therefore, elucidating the impact on macrophage polarization with CBD pre-treatment is necessary to understand its anti-inflammatory mechanisms. To study this effect, murine macrophages (RAW 264.7) were pre-treated with CBD (10 µM) or vehicle (ethanol 0.1 %) and were either left untreated (naive; cell media only), or stimulated under M1 (IFN-γ + lipopolysaccharide, LPS) or M2a (IL-4) conditions for 24 hr. Cells were analyzed for macrophage polarization markers, and supernatants were analyzed for cytokines and chemokines. Immunofluorescence staining was performed on M1-polarized cells for the metalloprotease, tumor necrosis factor-α-converting enzyme (TACE), as this enzyme is responsible for the secretion of TNF-α. Overall results showed that CBD decreased several markers associated with the M1 phenotype while exhibiting less effects on the M2a phenotype. Significantly, under M1 conditions, CBD increased the percentage of intracellular and surface TNF-α but decreased secreted TNF-α. This phenomenon might be mediated by TACE as staining showed that CBD sequestered TACE intracellularly. CBD also prevented RelA nuclear translocation. These results suggest that CBD may exert its anti-inflammatory effects by reducing M1 polarization and decreasing TNF-α secretion via inappropriate localization of TACE and RelA.</p></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"397 ","pages":"Article 104812"},"PeriodicalIF":4.3,"publicationDate":"2024-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139498654","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

Upregulation of CD8+ regulatory T cells following liver-directed AAV gene therapy 肝脏定向 AAV 基因疗法后 CD8+ 调节性 T 细胞的上调

IF 4.3 4区医学

Cellular immunology Pub Date : 2024-01-13 DOI: 10.1016/j.cellimm.2024.104806

Cristina D. Gaddie , Kevin G. Senior , Christopher Chan , Brad E. Hoffman , Geoffrey D. Keeler

{"title":"Upregulation of CD8+ regulatory T cells following liver-directed AAV gene therapy","authors":"Cristina D. Gaddie , Kevin G. Senior , Christopher Chan , Brad E. Hoffman , Geoffrey D. Keeler","doi":"10.1016/j.cellimm.2024.104806","DOIUrl":"10.1016/j.cellimm.2024.104806","url":null,"abstract":"<div><p>Liver-directed AAV gene therapy represents a unique treatment modality for a host of diseases. This is due, in part, to the induction of tolerance to transgene products. Despite the plethora of recognized regulatory cells in the body, there is currently a lack of literature supporting the induction of non-CD4<sup>+</sup> regulatory cells following hepatic AAV gene transfer. In this work, we show that CD8<sup>+</sup> regulatory T cells are up-regulated in PBMCs of mice following capsid only and therapeutic transgene AAV administration. Further, we demonstrate that hepatic AAV gene transfer results in a significant increase in CD8<sup>+</sup> regulatory T cells following experimental autoimmune encephalomyelitis induction. Notably, this response occurred only in therapeutic vector treated animals, not capsid only controls. Understanding the role these cells play in treatment efficacy will result in the development of improved AAV vectors that take advantage of the full gamut of regulatory cells within the body.</p></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"397 ","pages":"Article 104806"},"PeriodicalIF":4.3,"publicationDate":"2024-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0008874924000091/pdfft?md5=5af61897d3bc203ac6d9ec559746b9d8&pid=1-s2.0-S0008874924000091-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139461194","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

Life-threatening infections in human newborns: Reconciling age-specific vulnerability and interindividual variability 人类新生儿中危及生命的感染：调和特定年龄的易感性和个体间的变异性

IF 4.3 4区医学

Cellular immunology Pub Date : 2024-01-13 DOI: 10.1016/j.cellimm.2024.104807

Alessandro Borghesi

引用次数: 0

PIM kinase inhibitor AZD1208 in conjunction with Th1 cytokines potentiate death of breast cancer cells in vitro while also maximizing suppression of tumor growth in vivo when combined with immunotherapy PIM 激酶抑制剂 AZD1208 与 Th1 细胞因子结合使用可增强体外乳腺癌细胞的杀伤力，同时与免疫疗法结合使用还能最大程度地抑制体内肿瘤的生长

IF 4.3 4区医学

Cellular immunology Pub Date : 2024-01-08 DOI: 10.1016/j.cellimm.2024.104805

Ariel Anwar , Carissa Lepore , Brian J. Czerniecki , Gary K. Koski , Loral E. Showalter

{"title":"PIM kinase inhibitor AZD1208 in conjunction with Th1 cytokines potentiate death of breast cancer cells in vitro while also maximizing suppression of tumor growth in vivo when combined with immunotherapy","authors":"Ariel Anwar , Carissa Lepore , Brian J. Czerniecki , Gary K. Koski , Loral E. Showalter","doi":"10.1016/j.cellimm.2024.104805","DOIUrl":"10.1016/j.cellimm.2024.104805","url":null,"abstract":"<div><p>PIM kinases are over-expressed by a number of solid malignancies including breast cancer, and are thought to regulate proliferation, survival, and resistance to treatment, making them attractive therapeutic targets. Because PIM kinases sit at the nexus of multiple oncodriver pathways, PIM antagonist drugs are being tested alone and in conjunction with other therapies to optimize outcomes. We therefore sought to test the combination of pharmacological PIM antagonism and Th1-associated immunotherapy. We show that the pan PIM antagonist, AZD1208, when combined in vitro with Th1 cytokines IFN-γ and TNF-α, potentiates metabolic suppression, overall cell death, and expression of apoptotic markers in human breast cancer cell lines of diverse phenotypes (HER-2<sup>pos</sup>/ER<sup>neg</sup>, HER-2<sup>pos</sup>/ER<sup>pos</sup> and triple-negative). Interestingly, AZD1208 was shown to moderately inhibit IFN-γ secretion by stimulated T lymphocytes of both human and murine origin, suggesting some inherent immunosuppressive activity of the drug. Nonetheless, when multiplexed therapies were tested in a murine model of HER-2<sup>pos</sup> breast cancer, combinations of HER-2 peptide-pulsed DCs and AZD1208, as well as recombinant IFN-γ plus AZD1208 significantly suppressed tumor outgrowth compared with single-treatment and control groups. These studies suggest that PIM antagonism may combine productively with certain immunotherapies to improve responsiveness.</p></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"397 ","pages":"Article 104805"},"PeriodicalIF":4.3,"publicationDate":"2024-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139409659","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

Response to “Letter to the Editor: SMAC mimetics inhibit human T cell proliferation and fail to augment type 1 cytokine responses” 回应 "致编辑的信：SMAC模拟物抑制人类T细胞增殖且不能增强1型细胞因子反应"

IF 4.3 4区医学

Cellular immunology Pub Date : 2024-01-01 DOI: 10.1016/j.cellimm.2023.104785

Susan Murray

引用次数: 0

Letter to the Editor: SMAC mimetics inhibit human T cell proliferation and fail to augment type 1 cytokine responses 致编辑的信:SMAC模拟物抑制人T细胞增殖，不能增强1型细胞因子反应。

IF 4.3 4区医学

Cellular immunology Pub Date : 2024-01-01 DOI: 10.1016/j.cellimm.2023.104772

Jean Bourhis , Xu-Shan Sun , Yungan Tao

引用次数: 0

Dexamethasone alleviates pulmonary sarcoidosis by regulating the TGF-β/Smad3 signaling to promote Th17/Treg cell rebalance 地塞米松通过调节 TGF-β/Smad3 信号促进 Th17/Treg 细胞恢复平衡来缓解肺肉样瘤病

IF 4.3 4区医学

Cellular immunology Pub Date : 2024-01-01 DOI: 10.1016/j.cellimm.2023.104781

Yu Zhang , Xuan Jiang , Qing Wang , Jiayi Wu , Juan Zhou

{"title":"Dexamethasone alleviates pulmonary sarcoidosis by regulating the TGF-β/Smad3 signaling to promote Th17/Treg cell rebalance","authors":"Yu Zhang , Xuan Jiang , Qing Wang , Jiayi Wu , Juan Zhou","doi":"10.1016/j.cellimm.2023.104781","DOIUrl":"10.1016/j.cellimm.2023.104781","url":null,"abstract":"<div><p>Pulmonary sarcoidosis is an immune-mediated disorder closely related to Th17/Treg cell imbalance. Dexamethasone has been shown to regulate inflammation and immune responses in sarcoidosis patients. However, the underlying mechanisms of dexamethasone regulating Th17/Treg balance in sarcoidosis remain elusive. Herein, we elucidated the function role of TGF-β/Smad3 signaling in pulmonary sarcoidosis development and explored the underlying mechanism of dexamethasone in treating pulmonary sarcoidosis. We found that the TGF-β/Smad3 pathway was inactivated in pulmonary sarcoidosis patients. <em>Propionibacterium acnes</em> (PA) induced mouse model was generated to investigate the function of TGF-β/Smad3 signaling <em>in vivo</em>. Data indicated that IL17A inhibition with neutralizing antibody and activation of TGF-β/Smad3 signaling with SRI-011381 alleviated granuloma formation in the sarcoidosis mouse model. Moreover, we revealed that the Th17/Treg cell ratio was increased with PA treatment in mouse bronchoalveolar lavage fluid (BALF) and peripheral blood. The concentration of cytokines produced by Th17 cells (IL-17A, IL-23) was up-regulated in the BALF of PA-treated mice, while those produced by Tregs (IL-10, TGF-β1) presented significant reduction. The treatment of IL-17A neutralizing antibody or SRI-011381 was demonstrated to rescue the PA-induced changes in the concentration of IL-17A, IL-23, IL-10, and TGF-β1. Additionally, we demonstrated that dexamethasone treatment activated the TGF-β/Smad3 signaling in the lung tissues of pulmonary sarcoidosis mice. Dexamethasone was also revealed to promote the rebalancing of the Th17/Treg ratio and attenuated the granuloma formation in pulmonary sarcoidosis. In conclusion, dexamethasone activates the TGF-β/Smad3 signaling and induces Th17/Treg rebalance, alleviating pulmonary sarcoidosis, which suggests the potential of dexamethasone in treating pulmonary sarcoidosis.</p></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"395 ","pages":"Article 104781"},"PeriodicalIF":4.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135372132","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

Concomitant assessment of PD-1 and CD56 expression identifies subsets of resting cord blood Vδ2 T cells with disparate cytotoxic potential 同时评估 PD-1 和 CD56 表达可识别具有不同细胞毒性潜能的静息脐带血 Vδ2 T 细胞亚群

IF 4.3 4区医学

Cellular immunology Pub Date : 2024-01-01 DOI: 10.1016/j.cellimm.2023.104797

Haoting Hsu , Claudio Zanettini , Modupe Coker , Sarah Boudova , David Rach , Godfrey Mvula , Titus H. Divala , Randy G. Mungwira , Francesca Boldrin , Giulia Degiacomi , Laura Cioetto Mazzabò , Riccardo Manganelli , Miriam K. Laufer , Yuji Zhang , Luigi Marchionni , Cristiana Cairo

{"title":"Concomitant assessment of PD-1 and CD56 expression identifies subsets of resting cord blood Vδ2 T cells with disparate cytotoxic potential","authors":"Haoting Hsu , Claudio Zanettini , Modupe Coker , Sarah Boudova , David Rach , Godfrey Mvula , Titus H. Divala , Randy G. Mungwira , Francesca Boldrin , Giulia Degiacomi , Laura Cioetto Mazzabò , Riccardo Manganelli , Miriam K. Laufer , Yuji Zhang , Luigi Marchionni , Cristiana Cairo","doi":"10.1016/j.cellimm.2023.104797","DOIUrl":"10.1016/j.cellimm.2023.104797","url":null,"abstract":"<div><p>Vγ9Vδ2 T lymphocytes are programmed for broad antimicrobial responses with rapid production of Th1 cytokines even before birth, and thus thought to play key roles against pathogens in infants. The process regulating Vδ2 cell acquisition of cytotoxic potential shortly after birth remains understudied. We observed that perforin production in cord blood Vδ2 cells correlates with phenotypes defined by the concomitant assessment of PD-1 and CD56. Bulk RNA sequencing of sorted Vδ2 cell fractions indicated that transcripts related to cytotoxic activity and NK function are enriched in the subset with the highest proportion of perforin<sup>+</sup> cells. Among differentially expressed transcripts, IRF8, previously linked to CD8 T cell effector differentiation and NK maturation, has the potential to mediate Vδ2 cell differentiation towards cytotoxic effectors. Our current and past results support the hypothesis that distinct mechanisms regulate Vδ2 cell cytotoxic function before and after birth, possibly linked to different levels of microbial exposure.</p></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"395 ","pages":"Article 104797"},"PeriodicalIF":4.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139035756","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

Development of a highly cytotoxic, clinical-grade virus-specific T cell product for adoptive T cell therapy 开发用于采用 T 细胞疗法的高细胞毒性临床级病毒特异性 T 细胞产品

IF 4.3 4区医学

Cellular immunology Pub Date : 2023-12-10 DOI: 10.1016/j.cellimm.2023.104795

Fernanda Agostini Rocha , Caio Raony Farina Silveira , Ancély Ferreira dos Santos , Ana Carolina Buzzo Stefanini , Nelson Hamerschlak , Luciana Cavalheiro Marti

{"title":"Development of a highly cytotoxic, clinical-grade virus-specific T cell product for adoptive T cell therapy","authors":"Fernanda Agostini Rocha , Caio Raony Farina Silveira , Ancély Ferreira dos Santos , Ana Carolina Buzzo Stefanini , Nelson Hamerschlak , Luciana Cavalheiro Marti","doi":"10.1016/j.cellimm.2023.104795","DOIUrl":"10.1016/j.cellimm.2023.104795","url":null,"abstract":"<div><p>At present, recipients of allogeneic hematopoietic stem-cells are still suffering from recurrent infections after transplantation. Infusion of virus-specific T cells (VST) post-transplant reportedly fights several viruses without increasing the risk of <em>de novo</em> graft-<em>versus</em>-host disease. This study targeted cytomegalovirus (CMV) for the development of an innovative approach for generating a very specific VST product following Good Manufacturing Practices (GMP) guidelines.</p><p>We used a sterile disposable compartment named the Leukoreduction System Chamber (LRS-chamber) from the apheresis platelet donation kit as the starting material, which has demonstrated high levels of T cells. Using a combination of IL-2 and IL-7 we could improve expansion of CMV-specific T cells. Moreover, by developing and establishing a new product protocol, we were able to stimulate VST proliferation and favors T cell effector memory profile. The expanded VST were enriched in a closed automated system, creating a highly pure anti-CMV product, which was pre-clinically tested for specificity <em>in vitro</em> and for persistence, biodistribution, and toxicity <em>in vivo</em> using NOD scid mice. Our results demonstrated very specific VST, able to secrete high amounts of interferon only in the presence of cells infected by the human CMV strain (AD169), and innocuous to cells partially HLA compatible without viral infection.</p></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"395 ","pages":"Article 104795"},"PeriodicalIF":4.3,"publicationDate":"2023-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138567560","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