首页 > 最新文献

Cellular immunology最新文献

英文 中文
Variability of vaccine responsiveness in early life 早期疫苗反应性的变异性。
IF 4.3 4区 医学 Q2 CELL BIOLOGY Pub Date : 2023-10-15 DOI: 10.1016/j.cellimm.2023.104777
Michael E Pichichero

Vaccinations in early life elicit variable antibody and cellular immune responses, sometimes leaving fully vaccinated children unprotected against life-threatening infectious diseases. Specific immune cell populations and immune networks may have a critical period of development and calibration in a window of opportunity occurring during the first 100 days of early life. Among the early life determinants of vaccine responses, this review will focus on modifiable factors involving development of the infant microbiota and metabolome: antibiotic exposure, breast versus formula feeding, and Caesarian section versus vaginal delivery of newborns. How microbiota may serve as natural adjuvants for vaccine responses and how microbiota-derived metabolites influence vaccine responses are also reviewed. Early life poor vaccine responsiveness can be linked to increased infection susceptibility because both phenotypes share similar immunity dysregulation profiles. An early life pre-vaccination endotype, when interventions have the highest potential for success, should be sought that predicts vaccine response trajectories.

早期接种疫苗会引发可变的抗体和细胞免疫反应,有时会使完全接种疫苗的儿童无法抵御危及生命的传染病。特定的免疫细胞群和免疫网络可能在早期生命的前100天出现的机会窗口中有一个关键的发展和校准期。在疫苗反应的早期生命决定因素中,本综述将重点关注涉及婴儿微生物群和代谢组发育的可改变因素:抗生素暴露、母乳喂养与配方奶粉喂养以及新生儿剖腹产与阴道分娩。还综述了微生物群如何作为疫苗反应的天然佐剂,以及微生物群衍生的代谢物如何影响疫苗反应。早期疫苗反应性差可能与感染易感性增加有关,因为这两种表型具有相似的免疫失调特征。当干预措施具有最高成功潜力时,应寻求一种早期疫苗接种前的内型,以预测疫苗反应轨迹。
{"title":"Variability of vaccine responsiveness in early life","authors":"Michael E Pichichero","doi":"10.1016/j.cellimm.2023.104777","DOIUrl":"10.1016/j.cellimm.2023.104777","url":null,"abstract":"<div><p>Vaccinations in early life elicit variable antibody and cellular immune responses, sometimes leaving fully vaccinated children unprotected against life-threatening infectious diseases. Specific immune cell populations and immune networks may have a critical period of development and calibration in a window of opportunity occurring during the first 100 days of early life. Among the early life determinants of vaccine responses, this review will focus on modifiable factors involving development of the infant microbiota and metabolome: antibiotic exposure, breast versus formula feeding, and Caesarian section versus vaginal delivery of newborns. How microbiota may serve as natural adjuvants for vaccine responses and how microbiota-derived metabolites influence vaccine responses are also reviewed. Early life poor vaccine responsiveness can be linked to increased infection susceptibility because both phenotypes share similar immunity dysregulation profiles. An early life pre-vaccination endotype, when interventions have the highest potential for success, should be sought that predicts vaccine response trajectories.</p></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"393 ","pages":"Article 104777"},"PeriodicalIF":4.3,"publicationDate":"2023-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49688902","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
Ferroptosis in the post-transplantation inflammatory response 移植后炎症反应中的铁下垂。
IF 4.3 4区 医学 Q2 CELL BIOLOGY Pub Date : 2023-10-07 DOI: 10.1016/j.cellimm.2023.104774
Yun Zhu Bai , Benjamin J. Kopecky , Kory J. Lavine , Daniel Kreisel

Transplantation is a life-saving therapy for patients with end-stage organ disease. Successful outcomes after transplantation require mitigation of the post-transplant inflammatory response, limiting alloreactivity, and prevention of organ rejection. Traditional immunosuppressive regimens aim to dampen the adaptive immune response; however, recent studies have shown the feasibility and efficacy of targeting the innate immune response. Necroinflammation initiated by donor organ cell death is implicated as a critical mediator of primary graft dysfunction, acute rejection, and chronic rejection. Ferroptosis is a form of regulated cell death that triggers post-transplantation inflammation and drives the activation of both innate and adaptive immune cells. There is a growing acceptance of the clinical relevance of ferroptosis to solid organ transplantation. Modulating ferroptosis may be a potentially promising strategy to reduce complications after organ transplantation.

对于终末期器官疾病患者来说,移植是一种拯救生命的治疗方法。移植后的成功结果需要缓解移植后的炎症反应,限制同种异体反应,并预防器官排斥反应。传统的免疫抑制方案旨在抑制适应性免疫反应;然而,最近的研究已经表明了针对先天免疫反应的可行性和有效性。供体器官细胞死亡引发的坏死炎症是原发性移植物功能障碍、急性排斥反应和慢性排斥反应的关键介质。脱铁症是一种受调节的细胞死亡形式,它会引发移植后炎症,并驱动先天免疫细胞和适应性免疫细胞的激活。人们越来越接受脱铁性贫血与实体器官移植的临床相关性。调节脱铁性贫血可能是减少器官移植后并发症的一种潜在的有前景的策略。
{"title":"Ferroptosis in the post-transplantation inflammatory response","authors":"Yun Zhu Bai ,&nbsp;Benjamin J. Kopecky ,&nbsp;Kory J. Lavine ,&nbsp;Daniel Kreisel","doi":"10.1016/j.cellimm.2023.104774","DOIUrl":"10.1016/j.cellimm.2023.104774","url":null,"abstract":"<div><p>Transplantation is a life-saving therapy for patients with end-stage organ disease. Successful outcomes after transplantation require mitigation of the post-transplant inflammatory response, limiting alloreactivity, and prevention of organ rejection. Traditional immunosuppressive regimens aim to dampen the adaptive immune response; however, recent studies have shown the feasibility and efficacy of targeting the innate immune response. Necroinflammation initiated by donor organ cell death is implicated as a critical mediator of primary graft dysfunction, acute rejection, and chronic rejection. Ferroptosis is a form of regulated cell death that triggers post-transplantation inflammation and drives the activation of both innate and adaptive immune cells. There is a growing acceptance of the clinical relevance of ferroptosis to solid organ transplantation. Modulating ferroptosis may be a potentially promising strategy to reduce complications after organ transplantation.</p></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"393 ","pages":"Article 104774"},"PeriodicalIF":4.3,"publicationDate":"2023-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41232644","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
ATM-AMPKα mediated LAG-3 expression suppresses T cell function in prostate cancer ATM-AMPKα介导的LAG-3表达抑制癌症前列腺T细胞功能。
IF 4.3 4区 医学 Q2 CELL BIOLOGY Pub Date : 2023-09-28 DOI: 10.1016/j.cellimm.2023.104773
Xinyao Zhang , Haiqi Chen , Jiawen Han , Zongren Wang , Yu Guo , Zhongyang Zhou , Rong Luo , Meiqin Dai , Wei Ou , Lingwu Chen , Lan Shao

Immunotherapy for prostate cancer (PCa) faces serious challenges. Therefore, the co-inhibitory receptors that regulate T cell function of PCa must be elucidated. Here we identified that the inhibitory receptor LAG3 was significantly induced in T cells from PCa patients. Gene array analysis revealed that insufficient ataxia telangiectasia mutated (ATM) gene expression in PCa T cells was responsible for the elevated LAG3 expression. Mechanistically, insufficient ATM expression impaired its ability to activate AMPKα signaling and CD4+ T cell functions, which further enhances the binding of the transcription factors XBP1 and EGR2 to LAG3 promoter. Reconstitution of ATM and inhibition of XBP1 or EGR2 in PCa T cells suppressed LAG3 expression and restored the effector function of CD4+ T cells from PCa. Our study revealed the mechanism of LAG3 upregulation in CD4+ T lymphocytes of PCa patients and may provide insights for the development of immunotherapeutic strategies for PCa treatment.

癌症的免疫治疗面临着严峻的挑战。因此,必须阐明调节前列腺癌T细胞功能的共抑制受体。在这里,我们发现抑制性受体LAG3在前列腺癌患者的T细胞中被显著诱导。基因阵列分析显示,PCa T细胞中共济失调-毛细血管扩张症突变(ATM)基因表达不足是LAG3表达升高的原因。从机制上讲,ATM表达不足削弱了其激活AMPKα信号传导和CD4+T细胞功能的能力,这进一步增强了转录因子XBP1和EGR2与LAG3启动子的结合。PCa T细胞中ATM的重组和XBP1或EGR2的抑制抑制了LAG3的表达,并恢复了来自PCa的CD4+T细胞的效应器功能。我们的研究揭示了前列腺癌患者CD4+T淋巴细胞LAG3上调的机制,并可能为开发前列腺癌治疗的免疫治疗策略提供见解。
{"title":"ATM-AMPKα mediated LAG-3 expression suppresses T cell function in prostate cancer","authors":"Xinyao Zhang ,&nbsp;Haiqi Chen ,&nbsp;Jiawen Han ,&nbsp;Zongren Wang ,&nbsp;Yu Guo ,&nbsp;Zhongyang Zhou ,&nbsp;Rong Luo ,&nbsp;Meiqin Dai ,&nbsp;Wei Ou ,&nbsp;Lingwu Chen ,&nbsp;Lan Shao","doi":"10.1016/j.cellimm.2023.104773","DOIUrl":"10.1016/j.cellimm.2023.104773","url":null,"abstract":"<div><p>Immunotherapy for prostate cancer (PCa) faces serious challenges. Therefore, the co-inhibitory receptors that regulate T cell function of PCa must be elucidated. Here we identified that the inhibitory receptor LAG3 was significantly induced in T cells from PCa patients. Gene array analysis revealed that insufficient ataxia telangiectasia mutated (ATM) gene expression in PCa T cells was responsible for the elevated LAG3 expression. Mechanistically, insufficient ATM expression impaired its ability to activate AMPKα signaling and CD4<sup>+</sup> T cell functions, which further enhances the binding of the transcription factors XBP1 and EGR2 to <em>LAG3</em> promoter. Reconstitution of ATM and inhibition of XBP1 or EGR2 in PCa T cells suppressed LAG3 expression and restored the effector function of CD4<sup>+</sup> T cells from PCa. Our study revealed the mechanism of LAG3 upregulation in CD4<sup>+</sup> T lymphocytes of PCa patients and may provide insights for the development of immunotherapeutic strategies for PCa treatment.</p></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"393 ","pages":"Article 104773"},"PeriodicalIF":4.3,"publicationDate":"2023-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49674772","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
Early-immune development in asthma: A review of the literature 哮喘的早期免疫发展:文献综述。
IF 4.3 4区 医学 Q2 CELL BIOLOGY Pub Date : 2023-09-28 DOI: 10.1016/j.cellimm.2023.104770
Maria V. Medeleanu , Yu Chen Qian , Theo J. Moraes , Padmaja Subbarao

This review presents a comprehensive examination of the various factors contributing to the immunopathogenesis of asthma from the prenatal to preschool period. We focus on the contributions of genetic and environmental components as well as the role of the nasal and gut microbiome on immune development. Predisposing genetic factors, including inherited genes associated with increased susceptibility to asthma, are discussed alongside environmental factors such as respiratory viruses and pollutant exposure, which can trigger or exacerbate asthma symptoms. Furthermore, the intricate interplay between the nasal and gut microbiome and the immune system is explored, emphasizing their influence on allergic immune development and response to environmental stimuli. This body of literature underscores the necessity of a comprehensive approach to comprehend and manage asthma, as it emphasizes the interactions of multiple factors in immune development and disease progression.

本文综述了从产前到学龄前哮喘免疫发病的各种因素。我们关注基因和环境成分的贡献,以及鼻腔和肠道微生物组在免疫发育中的作用。易感遗传因素,包括与哮喘易感性增加相关的遗传基因,与环境因素(如呼吸道病毒和污染物暴露)一起讨论,这些因素可能引发或加剧哮喘症状。此外,还探讨了鼻腔和肠道微生物组与免疫系统之间复杂的相互作用,强调了它们对过敏性免疫发育和对环境刺激的反应的影响。这一系列文献强调了理解和管理哮喘的全面方法的必要性,因为它强调了免疫发展和疾病进展中多种因素的相互作用。
{"title":"Early-immune development in asthma: A review of the literature","authors":"Maria V. Medeleanu ,&nbsp;Yu Chen Qian ,&nbsp;Theo J. Moraes ,&nbsp;Padmaja Subbarao","doi":"10.1016/j.cellimm.2023.104770","DOIUrl":"10.1016/j.cellimm.2023.104770","url":null,"abstract":"<div><p>This review presents a comprehensive examination of the various factors contributing to the immunopathogenesis of asthma from the prenatal to preschool period. We focus on the contributions of genetic and environmental components as well as the role of the nasal and gut microbiome on immune development. Predisposing genetic factors, including inherited genes associated with increased susceptibility to asthma, are discussed alongside environmental factors such as respiratory viruses and pollutant exposure, which can trigger or exacerbate asthma symptoms. Furthermore, the intricate interplay between the nasal and gut microbiome and the immune system is explored, emphasizing their influence on allergic immune development and response to environmental stimuli. This body of literature underscores the necessity of a comprehensive approach to comprehend and manage asthma, as it emphasizes the interactions of multiple factors in immune development and disease progression.</p></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"393 ","pages":"Article 104770"},"PeriodicalIF":4.3,"publicationDate":"2023-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41192827","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
Interactions of mesenchymal stromal/stem cells and immune cells following MSC-based therapeutic approaches in rheumatoid arthritis 基于MSC的类风湿性关节炎治疗方法后间充质基质/干细胞和免疫细胞的相互作用。
IF 4.3 4区 医学 Q2 CELL BIOLOGY Pub Date : 2023-09-22 DOI: 10.1016/j.cellimm.2023.104771
Sajad Dehnavi , Mahvash Sadeghi , Jalil Tavakol Afshari , Mojgan Mohammadi

Rheumatoid arthritis (RA) is considered to be a degenerative and progressive autoimmune disorder. Although several medicinal regimens are used to treat RA, potential adverse events such as metabolic disorders and increased risk of infection, as well as drug resistance in some patients, make it essential to find an effective and safe therapeutic approach. Mesenchymal stromal/stem cells (MSCs) are a group of non-hematopoietic stromal cells with immunomodulatory and inhibitory potential. These cells exert their regulatory properties through direct cell-to-cell interactions and paracrine effects on various immune and non-immune cells. As conventional therapeutic approaches for RA are limited due to their side effects, and some patients became refractory to the treatment, MSCs are considered as a promising alternative treatment for RA. In this review, we introduced various experimental and clinical studies conducted to evaluate the therapeutic effects of MSCs on animal models of arthritis and RA patients. Then, possible modulatory and suppressive effects of MSCs on different innate and adaptive immune cells, including dendritic cells, neutrophils, macrophages, natural killer cells, B lymphocytes, and various subtypes of T cells, were categorized and summarized. Finally, limitations and future considerations for the efficient application of MSCs as a therapeutic approach in RA patients were presented.

类风湿性关节炎(RA)被认为是一种退行性和进行性自身免疫性疾病。尽管有几种药物方案用于治疗RA,但潜在的不良事件,如代谢紊乱和感染风险增加,以及一些患者的耐药性,使得找到有效和安全的治疗方法至关重要。间充质基质/干细胞是一组具有免疫调节和抑制潜力的非造血基质细胞。这些细胞通过直接的细胞间相互作用和对各种免疫细胞和非免疫细胞的旁分泌作用发挥其调节特性。由于RA的传统治疗方法因其副作用而受到限制,并且一些患者对治疗变得难治,MSCs被认为是RA的一种有前途的替代治疗方法。在这篇综述中,我们介绍了各种实验和临床研究,以评估骨髓间充质干细胞对关节炎和RA患者动物模型的治疗效果。然后,对MSCs对不同先天和适应性免疫细胞的可能调节和抑制作用进行了分类和总结,包括树突状细胞、中性粒细胞、巨噬细胞、自然杀伤细胞、B淋巴细胞和各种亚型的T细胞。最后,介绍了骨髓间充质干细胞作为RA患者有效治疗方法的局限性和未来的考虑因素。
{"title":"Interactions of mesenchymal stromal/stem cells and immune cells following MSC-based therapeutic approaches in rheumatoid arthritis","authors":"Sajad Dehnavi ,&nbsp;Mahvash Sadeghi ,&nbsp;Jalil Tavakol Afshari ,&nbsp;Mojgan Mohammadi","doi":"10.1016/j.cellimm.2023.104771","DOIUrl":"10.1016/j.cellimm.2023.104771","url":null,"abstract":"<div><p>Rheumatoid arthritis (RA) is considered to be a degenerative and progressive autoimmune disorder. Although several medicinal regimens are used to treat RA, potential adverse events such as metabolic disorders and increased risk of infection, as well as drug resistance in some patients, make it essential to find an effective and safe therapeutic approach. Mesenchymal stromal/stem cells (MSCs) are a group of non-hematopoietic stromal cells with immunomodulatory and inhibitory potential. These cells exert their regulatory properties through direct cell-to-cell interactions and paracrine effects on various immune and non-immune cells. As conventional therapeutic approaches for RA are limited due to their side effects, and some patients became refractory to the treatment, MSCs are considered as a promising alternative treatment for RA. In this review, we introduced various experimental and clinical studies conducted to evaluate the therapeutic effects of MSCs on animal models of arthritis and RA patients. Then, possible modulatory and suppressive effects of MSCs on different innate and adaptive immune cells, including dendritic cells, neutrophils, macrophages, natural killer cells, B lymphocytes, and various subtypes of T cells, were categorized and summarized. Finally, limitations and future considerations for the efficient application of MSCs as a therapeutic approach in RA patients were presented.</p></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"393 ","pages":"Article 104771"},"PeriodicalIF":4.3,"publicationDate":"2023-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41107003","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: 1
Serum IgA augments adhesiveness of cultured lung microvascular endothelial cells and suppresses angiogenesis 血清IgA增强培养的肺微血管内皮细胞的粘附性并抑制血管生成。
IF 4.3 4区 医学 Q2 CELL BIOLOGY Pub Date : 2023-09-16 DOI: 10.1016/j.cellimm.2023.104769
Kazufumi Takada , Maho Suzukawa , Sayaka Igarashi , Yuuki Uehara , Shizuka Watanabe , Sahoko Imoto , Masaki Ishii , Yoshiteru Morio , Hirotoshi Matsui , Masahiro Akishita , Ken Ohta

Immunoglobulin A (IgA) is important in local immunity and is also abundant in the blood. This study aimed to evaluate the effects of serum IgA on cultured lung microvascular endothelial cells (HMVEC-Ls), which are involved in the pathogenesis of inflammatory lung diseases. Serum IgA induced adhesion molecules and inflammatory cytokine production from HMVEC-Ls, and enhanced adhesion of peripheral blood mononuclear cells to HMVEC-Ls. In contrast, migration, proliferation, and tube formation of HMVEC-Ls were significantly suppressed by serum IgA. Experiments with siRNAs and western blotting revealed that two known IgA receptors, β1,4-galactosyltransferase 1 (b4GALT1) and asialoglycoprotein receptor 1 (ASGR1), and mitogen-activated protein kinase and nuclear factor-kappa B pathways were partly involved in serum IgA-induced cytokine production by HMVEC-Ls. Collectively, serum IgA enhanced cytokine production and adhesiveness of HMVEC-L, with b4GALT1 and ASGR1 partially being involved, and suppressed angiogenesis. Thus, serum IgA may be targeted to treat inflammatory lung diseases.

免疫球蛋白A(IgA)在局部免疫中很重要,在血液中也很丰富。本研究旨在评估血清IgA对培养的肺微血管内皮细胞(HMVEC Ls)的影响,这些细胞参与了炎症性肺部疾病的发病机制。血清IgA诱导HMVEC Ls产生粘附分子和炎性细胞因子,并增强外周血单核细胞与HMVEC L的粘附。相反,血清IgA显著抑制HMVEC Ls的迁移、增殖和管形成。siRNA和蛋白质印迹实验表明,两种已知的IgA受体,β1,4-半乳糖基转移酶1(b4GALT1)和去唾液酸糖蛋白受体1(ASGR1),以及促分裂原活化蛋白激酶和核因子κB途径,部分参与了HMVEC Ls产生血清IgA诱导的细胞因子。总的来说,血清IgA增强了细胞因子的产生和HMVEC-L的粘附性,b4GALT1和ASGR1部分参与其中,并抑制了血管生成。因此,血清IgA可以靶向治疗炎症性肺部疾病。
{"title":"Serum IgA augments adhesiveness of cultured lung microvascular endothelial cells and suppresses angiogenesis","authors":"Kazufumi Takada ,&nbsp;Maho Suzukawa ,&nbsp;Sayaka Igarashi ,&nbsp;Yuuki Uehara ,&nbsp;Shizuka Watanabe ,&nbsp;Sahoko Imoto ,&nbsp;Masaki Ishii ,&nbsp;Yoshiteru Morio ,&nbsp;Hirotoshi Matsui ,&nbsp;Masahiro Akishita ,&nbsp;Ken Ohta","doi":"10.1016/j.cellimm.2023.104769","DOIUrl":"10.1016/j.cellimm.2023.104769","url":null,"abstract":"<div><p>Immunoglobulin A (IgA) is important in local immunity and is also abundant in the blood. This study aimed to evaluate the effects of serum IgA on cultured lung microvascular endothelial cells (HMVEC-Ls), which are involved in the pathogenesis of inflammatory lung diseases. Serum IgA induced adhesion molecules and inflammatory cytokine production from HMVEC-Ls, and enhanced adhesion of peripheral blood mononuclear cells to HMVEC-Ls. In contrast, migration, proliferation, and tube formation of HMVEC-Ls were significantly suppressed by serum IgA. Experiments with siRNAs and western blotting revealed that two known IgA receptors, β1,4-galactosyltransferase 1 (b4GALT1) and asialoglycoprotein receptor 1 (ASGR1), and mitogen-activated protein kinase and nuclear factor-kappa B pathways were partly involved in serum IgA-induced cytokine production by HMVEC-Ls. Collectively, serum IgA enhanced cytokine production and adhesiveness of HMVEC-L, with b4GALT1 and ASGR1 partially being involved, and suppressed angiogenesis. Thus, serum IgA may be targeted to treat inflammatory lung diseases.</p></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"393 ","pages":"Article 104769"},"PeriodicalIF":4.3,"publicationDate":"2023-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41115511","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
PD-1 negatively tunes macrophage immune activation by turning off JNK and STAT1 signaling: Exploited by Leishmania for its intra-macrophage survival PD-1通过关闭JNK和STAT1信号通路负向调节巨噬细胞免疫激活:利什曼原虫利用其巨噬细胞内存活
IF 4.3 4区 医学 Q2 CELL BIOLOGY Pub Date : 2023-09-01 DOI: 10.1016/j.cellimm.2023.104758
Shalini Roy , Anand K Gupta , Madhurima Banerjee , Pijush K. Das , Anindita Ukil

The anti-inflammatory role of the programmed death-1 receptor (PD-1) is well appreciated. However, the mechanism of how PD-1 signaling inhibits the pro-inflammatory cytokine responses in macrophages, which is further exploited by Leishmania to foster their intracellular survival, was unknown. We found that among three major MAP kinases regulating immune activation, PD-1 signaling decreased only JNK phosphorylation without perturbing p38 and ERK. Inflammatory transcription factor STAT1 was also inhibited by PD-1. Association studies documented that SHP, the downstream phosphatase of PD-1, is directly responsible for the decreased phosphorylation of JNK and STAT1. JNK and STAT1 deactivation led to Elk-1/c-Fos inhibition, which significantly decreased IL-12 and TNF-α levels. Further investigation revealed c-Fos deactivation ultimately rendered transcription factor AP1 inactive and facilitating parasite-favorable anti-inflammatory environment.

程序性死亡-1受体(PD-1)的抗炎作用得到了很好的评价。然而,PD-1信号如何抑制巨噬细胞中的促炎细胞因子反应的机制尚不清楚,利什曼原虫进一步利用这种反应来促进其细胞内生存。我们发现,在调节免疫激活的三种主要MAP激酶中,PD-1信号仅降低JNK磷酸化,而不干扰p38和ERK。炎症转录因子STAT1也被PD-1抑制。关联研究表明,PD-1的下游磷酸酶SHP是JNK和STAT1磷酸化降低的直接原因。JNK和STAT1失活导致Elk-1/c-Fos抑制,显著降低IL-12和TNF-α水平。进一步的研究表明,c-Fos失活最终使转录因子AP1失活,并促进寄生虫有利的抗炎环境。
{"title":"PD-1 negatively tunes macrophage immune activation by turning off JNK and STAT1 signaling: Exploited by Leishmania for its intra-macrophage survival","authors":"Shalini Roy ,&nbsp;Anand K Gupta ,&nbsp;Madhurima Banerjee ,&nbsp;Pijush K. Das ,&nbsp;Anindita Ukil","doi":"10.1016/j.cellimm.2023.104758","DOIUrl":"10.1016/j.cellimm.2023.104758","url":null,"abstract":"<div><p>The anti-inflammatory role of the programmed death-1 receptor (PD-1) is well appreciated. However, the mechanism of how PD-1 signaling inhibits the pro-inflammatory cytokine responses in macrophages, which is further exploited by <em>Leishmania</em> to foster their intracellular survival, was unknown. We found that among three major MAP kinases regulating immune activation, PD-1 signaling decreased only JNK phosphorylation without perturbing p38 and ERK. Inflammatory transcription factor STAT1 was also inhibited by PD-1. Association studies documented that SHP, the downstream phosphatase of PD-1, is directly responsible for the decreased phosphorylation of JNK and STAT1. JNK and STAT1 deactivation led to Elk-1/c-Fos inhibition, which significantly decreased IL-12 and TNF-α levels. Further investigation revealed c-Fos deactivation ultimately rendered transcription factor AP1 inactive and facilitating parasite-favorable anti-inflammatory environment.</p></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"391 ","pages":"Article 104758"},"PeriodicalIF":4.3,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10314827","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
Editorial: Processing, presentation, and recognition of T cell determinants: From molecular insights to clinical applications 编辑:T细胞决定因子的处理、表现和识别:从分子洞察到临床应用
IF 4.3 4区 医学 Q2 CELL BIOLOGY Pub Date : 2023-09-01 DOI: 10.1016/j.cellimm.2023.104756
Eddie A. James
{"title":"Editorial: Processing, presentation, and recognition of T cell determinants: From molecular insights to clinical applications","authors":"Eddie A. James","doi":"10.1016/j.cellimm.2023.104756","DOIUrl":"10.1016/j.cellimm.2023.104756","url":null,"abstract":"","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"391 ","pages":"Article 104756"},"PeriodicalIF":4.3,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10260836","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
Haploinsufficiency of A20 caused by a novel pathogenic missense variant of TNFAIP3 and successfully treated with anti-TNF and immunosuppressive therapies 由一种新的致病性TNFAIP3错义变体引起的A20单倍性不足,并成功地通过抗tnf和免疫抑制疗法治疗
IF 4.3 4区 医学 Q2 CELL BIOLOGY Pub Date : 2023-09-01 DOI: 10.1016/j.cellimm.2023.104753
Sun Lina , Han Ya'nan , Yang Ying , Wang Fengfan , Hou Xin , Ren Xiaoxia , Fang Ying

Loss-of-function of protein A20, encoded by TNFAIP3, leads to an early-onset haploinsufficiency of A20 (HA20). This study reports one Chinese child with HA20 and explores the genetic etiology of TNFAIP3 variant. The patient exhibited transient recurrent episodes of fever, intermittent signs of arthritis, gastrointestinal symptoms and multiple colonic ulcers. Laboratory tests revealed elevated inflammatory indicators and mild to moderate anemia. Genetic analysis identified a heterozygous de novo variant in his TNFAIP3 gene (c.740C>T, p. P247L), which had never been reported before. The novel missense variation was validated to be pathogenic through causing insufficient expression of A20, over-activation of NF-κB signaling pathway and elevated levels of proinflammatory cytokines in response to stimulation by lipopolysaccharide. A combination of oral corticosteroids, TNF-α inhibitors and thalidomide freed him from symptoms and abnormal inflammatory indicators. Furthermore, continual improvement of the patient's condition was observed during a follow-up period of five months. We demonstrate a case with a de novo missense variant resulting in a loss-of-function of TNFAIP3, which expands the clinical spectrum of HA20. Cytokine antagonists and immunosuppressants may be effective drugs.

由TNFAIP3编码的A20蛋白功能的丧失导致A20(HA20)早发性单倍性不足。本研究报告了一名患有HA20的中国儿童,并探讨了TNFAIP3变体的遗传病因。患者表现出短暂的反复发热、关节炎的间歇性症状、胃肠道症状和多发性结肠溃疡。实验室检查显示炎症指标升高和轻度至中度贫血。遗传分析在他的TNFAIP3基因中发现了一个杂合的从头变异(c.740C>T,p.P247L),这在以前从未报道过。通过引起A20表达不足、NF-κB信号通路过度激活和脂多糖刺激后促炎细胞因子水平升高,这种新的错义变异被证实是致病性的。口服皮质类固醇、TNF-α抑制剂和沙利度胺使他摆脱了症状和异常炎症指标。此外,在五个月的随访期间,观察到患者的病情持续改善。我们证明了一个新的错义变体导致TNFAIP3功能丧失的病例,这扩大了HA20的临床谱。细胞因子拮抗剂和免疫抑制剂可能是有效的药物。
{"title":"Haploinsufficiency of A20 caused by a novel pathogenic missense variant of TNFAIP3 and successfully treated with anti-TNF and immunosuppressive therapies","authors":"Sun Lina ,&nbsp;Han Ya'nan ,&nbsp;Yang Ying ,&nbsp;Wang Fengfan ,&nbsp;Hou Xin ,&nbsp;Ren Xiaoxia ,&nbsp;Fang Ying","doi":"10.1016/j.cellimm.2023.104753","DOIUrl":"10.1016/j.cellimm.2023.104753","url":null,"abstract":"<div><p>Loss-of-function of protein A20, encoded by <em>TNFAIP3</em>, leads to an early-onset haploinsufficiency of A20 (HA20). This study reports one Chinese child with HA20 and explores the genetic etiology of <em>TNFAIP3</em> variant. The patient exhibited transient recurrent episodes of fever, intermittent signs of arthritis, gastrointestinal symptoms and multiple colonic ulcers. Laboratory tests revealed elevated inflammatory indicators and mild to moderate anemia. Genetic analysis identified a heterozygous <em>de novo</em> variant in his <em>TNFAIP3</em> gene (c.740C>T, p. P247L), which had never been reported before. The novel missense variation was validated to be pathogenic through causing insufficient expression of A20, over-activation of NF-κB signaling pathway and elevated levels of proinflammatory cytokines in response to stimulation by lipopolysaccharide. A combination of oral corticosteroids, TNF-α inhibitors and thalidomide freed him from symptoms and abnormal inflammatory indicators. Furthermore, continual improvement of the patient's condition was observed during a follow-up period of five months. We demonstrate a case with a <em>de novo</em> missense variant resulting in a loss-of-function of <em>TNFAIP3</em>, which expands the clinical spectrum of HA20. Cytokine antagonists and immunosuppressants may be effective drugs.</p></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"391 ","pages":"Article 104753"},"PeriodicalIF":4.3,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10260807","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
Attenuated airways inflammation and remodeling in IL-37a and IL-37b transgenic mice with an ovalbumin-induced chronic asthma IL-37a和IL-37b转基因小鼠卵清蛋白诱导的慢性哮喘气道炎症和重塑
IF 4.3 4区 医学 Q2 CELL BIOLOGY Pub Date : 2023-09-01 DOI: 10.1016/j.cellimm.2023.104759
Lele Cui , Xiaofeng Qin , Tingting Fu , Chenduo Li , Dan Wang , Yue Hu , Yan Li , Yan Chen , Ye Cui , Jingjing Wang , Huihui Yuan , Zhe Lv , Jie Liu , Damo Xu , Rongfei Wei , Sun Ying , Wei Wang

Background

Asthma is a common chronic respiratory disease characterized by airways inflammation, hyperresponsiveness and remodeling. IL-37, an anti-inflammatory cytokine, consists of five splice isoforms, that is, a-e. Although it has been previously shown that recombinant human IL-37b is able to inhibit airway inflammation and hyperresponsiveness in animal models of asthma, the effects and difference of other IL-37 isoforms, such as IL-37a on features of asthma are unknown.

Methods

Animal models of chronic asthma were established using IL-37a and IL-37b transgenic mice with C57BL/6J background and wild-type (WT) mice sensitized and nasally challenged with ovalbumin (OVA). Airway hyperresponsiveness was measured using FlexiVent apparatus, while histological and immunohistological stainings were employed to measure airways inflammation and remodeling indexes, including goblet cell metaplasia, mucus production, deposition of collagen, hypertrophy of airway smooth muscles and pulmonary angiogenesis.

Results

Compared to WT mice, both IL-37a and IL-37b transgenic mice had significant reduced airway hyperresponsiveness and the declined total numbers of inflammatory cells, predominant eosinophils into airways and lung tissues. Furthermore, all features of airways remodeling, including degrees of mucus expression, collagen deposition, hypertrophy of smooth muscles, thickness of airways and neovascularization markedly decreased in IL-37 transgenic mice compared with OVA-treated WT mice.

Conclusion

Our data suggest that both IL-37a and IL-37b isoforms are able to not only ameliorate airways inflammation and airways hyperresponsiveness, but also greatly reduce airways structural changes of animal models of chronic asthma.

背景哮喘是一种常见的慢性呼吸道疾病,以气道炎症、高反应性和重塑为特征。IL-37是一种抗炎细胞因子,由五种剪接异构体组成,即a-e。尽管先前已经表明重组人IL-37b能够在哮喘动物模型中抑制气道炎症和高反应性,但其他IL-37亚型(如IL-37a)对哮喘特征的影响和差异尚不清楚。方法采用C57BL/6J背景的IL-37a和IL-37b转基因小鼠和卵清蛋白(OVA)致敏和鼻激发的野生型(WT)小鼠建立慢性哮喘动物模型。使用FlexiVent设备测量气道高反应性,同时使用组织学和免疫组织学染色来测量气道炎症和重塑指数,包括杯状细胞化生、粘液产生、胶原沉积、气道平滑肌肥大和肺血管生成。结果与野生型小鼠相比,IL-37a和IL-37b转基因小鼠的气道高反应性显著降低,炎症细胞总数下降,主要是进入气道和肺组织的嗜酸性粒细胞。此外,与OVA处理的WT小鼠相比,IL-37转基因小鼠的气道重塑的所有特征,包括粘液表达程度、胶原沉积、平滑肌肥大、气道厚度和新生血管形成,都显著降低。结论IL-37a和IL-37b亚型均能改善慢性哮喘动物模型的气道炎症和气道高反应性,并能显著减少气道结构变化。
{"title":"Attenuated airways inflammation and remodeling in IL-37a and IL-37b transgenic mice with an ovalbumin-induced chronic asthma","authors":"Lele Cui ,&nbsp;Xiaofeng Qin ,&nbsp;Tingting Fu ,&nbsp;Chenduo Li ,&nbsp;Dan Wang ,&nbsp;Yue Hu ,&nbsp;Yan Li ,&nbsp;Yan Chen ,&nbsp;Ye Cui ,&nbsp;Jingjing Wang ,&nbsp;Huihui Yuan ,&nbsp;Zhe Lv ,&nbsp;Jie Liu ,&nbsp;Damo Xu ,&nbsp;Rongfei Wei ,&nbsp;Sun Ying ,&nbsp;Wei Wang","doi":"10.1016/j.cellimm.2023.104759","DOIUrl":"10.1016/j.cellimm.2023.104759","url":null,"abstract":"<div><h3>Background</h3><p>Asthma is a common chronic respiratory disease characterized by airways inflammation, hyperresponsiveness and remodeling. IL-37, an anti-inflammatory cytokine, consists of five splice isoforms, that is, a-e. Although it has been previously shown that recombinant human IL-37b is able to inhibit airway inflammation and hyperresponsiveness in animal models of asthma, the effects and difference of other IL-37 isoforms, such as IL-37a on features of asthma are unknown.</p></div><div><h3>Methods</h3><p>Animal models of chronic asthma were established using IL-37a and IL-37b transgenic mice with C57BL/6J background and wild-type (WT) mice sensitized and nasally challenged with ovalbumin (OVA). Airway hyperresponsiveness was measured using FlexiVent apparatus, while histological and immunohistological stainings were employed to measure airways inflammation and remodeling indexes, including goblet cell metaplasia, mucus production, deposition of collagen, hypertrophy of airway smooth muscles and pulmonary angiogenesis.</p></div><div><h3>Results</h3><p>Compared to WT mice, both IL-37a and IL-37b transgenic mice had significant reduced airway hyperresponsiveness and the declined total numbers of inflammatory cells, predominant eosinophils into airways and lung tissues. Furthermore, all features of airways remodeling, including degrees of mucus expression, collagen deposition, hypertrophy of smooth muscles, thickness of airways and neovascularization markedly decreased in IL-37 transgenic mice compared with OVA-treated WT mice.</p></div><div><h3>Conclusion</h3><p>Our data suggest that both IL-37a and IL-37b isoforms are able to not only ameliorate airways inflammation and airways hyperresponsiveness, but also greatly reduce airways structural changes of animal models of chronic asthma.</p></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"391 ","pages":"Article 104759"},"PeriodicalIF":4.3,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10261900","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
期刊
Cellular immunology
全部 Acc. Chem. Res. ACS Applied Bio Materials ACS Appl. Electron. Mater. ACS Appl. Energy Mater. ACS Appl. Mater. Interfaces ACS Appl. Nano Mater. ACS Appl. Polym. Mater. ACS BIOMATER-SCI ENG ACS Catal. ACS Cent. Sci. ACS Chem. Biol. ACS Chemical Health & Safety ACS Chem. Neurosci. ACS Comb. Sci. ACS Earth Space Chem. ACS Energy Lett. ACS Infect. Dis. ACS Macro Lett. ACS Mater. Lett. ACS Med. Chem. Lett. ACS Nano ACS Omega ACS Photonics ACS Sens. ACS Sustainable Chem. Eng. ACS Synth. Biol. Anal. Chem. BIOCHEMISTRY-US Bioconjugate Chem. BIOMACROMOLECULES Chem. Res. Toxicol. Chem. Rev. Chem. Mater. CRYST GROWTH DES ENERG FUEL Environ. Sci. Technol. Environ. Sci. Technol. Lett. Eur. J. Inorg. Chem. IND ENG CHEM RES Inorg. Chem. J. Agric. Food. Chem. J. Chem. Eng. Data J. Chem. Educ. J. Chem. Inf. Model. J. Chem. Theory Comput. J. Med. Chem. J. Nat. Prod. J PROTEOME RES J. Am. Chem. Soc. LANGMUIR MACROMOLECULES Mol. Pharmaceutics Nano Lett. Org. Lett. ORG PROCESS RES DEV ORGANOMETALLICS J. Org. Chem. J. Phys. Chem. J. Phys. Chem. A J. Phys. Chem. B J. Phys. Chem. C J. Phys. Chem. Lett. Analyst Anal. Methods Biomater. Sci. Catal. Sci. Technol. Chem. Commun. Chem. Soc. Rev. CHEM EDUC RES PRACT CRYSTENGCOMM Dalton Trans. Energy Environ. Sci. ENVIRON SCI-NANO ENVIRON SCI-PROC IMP ENVIRON SCI-WAT RES Faraday Discuss. Food Funct. Green Chem. Inorg. Chem. Front. Integr. Biol. J. Anal. At. Spectrom. J. Mater. Chem. A J. Mater. Chem. B J. Mater. Chem. C Lab Chip Mater. Chem. Front. Mater. Horiz. MEDCHEMCOMM Metallomics Mol. Biosyst. Mol. Syst. Des. Eng. Nanoscale Nanoscale Horiz. Nat. Prod. Rep. New J. Chem. Org. Biomol. Chem. Org. Chem. Front. PHOTOCH PHOTOBIO SCI PCCP Polym. Chem.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1