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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 Immunology and Microbiology 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。
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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 Immunology and Microbiology 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。
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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 Immunology and Microbiology 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。
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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 Immunology and Microbiology 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。
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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 Immunology and Microbiology 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。
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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 Immunology and Microbiology Pub Date : 2023-09-01 DOI: 10.1016/j.cellimm.2023.104756
Eddie A. James
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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 Immunology and Microbiology 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。
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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 Immunology and Microbiology 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":null,"pages":null},"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
Piperine suppresses inflammatory fibroblast-like synoviocytes derived from rheumatoid arthritis patients Via NF-κB inhibition 胡椒碱通过抑制NF-κB抑制类风湿关节炎患者炎性成纤维细胞样滑膜细胞
IF 4.3 4区 医学 Q2 Immunology and Microbiology Pub Date : 2023-09-01 DOI: 10.1016/j.cellimm.2023.104752
Qoyama Noel Baito, Halmat M. Jaafar, Talar Ahmad Merza Mohammad

Rheumatoid Arthritis (RA) is a common autoimmune disease recognized by hyperplasia of synoviocytes and chronic joint inflammation. Activation of fibroblast-like synoviocytes (FLSs) is one of the main features of RA which can trigger inflammation leading to articular cartilage and joint destruction. Aberrant activation of NF-κB signaling cascade was found to be responsible for the high proliferation and defective apoptosis of FLSs and subsequent inflammation in RA. Piperine is a principal constituent of piper species frequently used as antitumor and anti-inflammatory natural compound. In this study we aimed to assess the anti-inflammatory effect of piperine on RA-FLS through NF-κB inhibition.

FLSs were isolated from 68 RA patients and 30 healthy controls and were exposed to piperine. The main assays were MTT assay, flow cytometric analysis, PI staining, reverse transcription-PCR (RT-PCR), and ELISA.

Results showed that piperine can induce the apoptosis and reduce the proliferation of RA-FLSs in vitro. Moreover, piperine directly reduced the phosphorylation of NF-kB and the expression of NF-κB target genes related to RA-FLSs proliferation (c-Myc and Cycline D1), apoptosis inhibition (Bcl2 and Bcl-xl) and inflammation (COX2, IL-1β, TNF-α,IL-6, CCL5 and CXCL10) while increasing the expression of apoptosis related ones (Bax) in vitro. Piperine also reduced the protein levels of cytokines and chemokines secreted by FLSs as a result of NF-κB inhibition.

In conclusion, our results provide evidence for the anti-inflammatory capacity of piperine through inhibition of NF-κB pathway in FLSs proposing this compound as a suitable alternative for chemical treatment of RA.

类风湿性关节炎(RA)是一种常见的自身免疫性疾病,由滑膜细胞增生和慢性关节炎症引起。成纤维细胞样滑膜细胞(FLSs)的激活是RA的主要特征之一,可引发炎症,导致关节软骨和关节破坏。NF-κB信号级联的异常激活被发现是FLSs的高增殖和缺陷性凋亡以及随后RA炎症的原因。胡椒碱是胡椒属植物的主要成分,常用作抗肿瘤和抗炎的天然化合物。在本研究中,我们旨在通过抑制NF-κB来评估胡椒碱对RA-FLS的抗炎作用。从68名RA患者和30名健康对照中分离出FLS,并暴露于胡椒碱。主要检测方法为MTT法、流式细胞仪、PI染色、逆转录聚合酶链式反应(RT-PCR)和ELISA。此外,哌啶在体外直接降低了NF-kB的磷酸化和NF-κB靶基因的表达,这些靶基因与RA FLSs增殖(c-Myc和Cycline D1)、细胞凋亡抑制(Bcl2和Bcl-xl)和炎症(COX2、IL-1β、TNF-α、IL-6、CCL5和CXCL10)有关,同时增加了细胞凋亡相关基因(Bax)的表达。胡椒碱还降低了FLSs分泌的细胞因子和趋化因子的蛋白质水平,这是NF-κB抑制的结果。总之,我们的研究结果通过抑制FLSs中的NF-κB途径为哌啶的抗炎能力提供了证据,提出该化合物是化学治疗RA的合适替代品。
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引用次数: 0
Crosstalk between peripheral immunity and central nervous system in Alzheimer’s disease 阿尔茨海默病中外周免疫与中枢神经系统的串扰
IF 4.3 4区 医学 Q2 Immunology and Microbiology Pub Date : 2023-09-01 DOI: 10.1016/j.cellimm.2023.104743
Hanchen Yang , Qi Qin , Meng Wang , Yunsi Yin , Ruiyang Li , Yi Tang

The significance of peripheral immunity in the pathogenesis and progression of Alzheimer’s diseases (AD) has been recognized. Brain-infiltrated peripheral immune components transporting across the blood–brain barrier (BBB) may reshape the central immune environment. However, mechanisms of how these components open the BBB for AD occurrence and development and correlations between peripheral and central immunity have not been fully explored. Herein, we formulate a hypothesis whereby peripheral immunity as a critical factor allows AD to progress. Peripheral central immune cell crosstalk is associated with early AD pathology and related risk factors. The damaged BBB permits peripheral immune cells to enter the central immune system to deprive its immune privilege promoting the progression toward developing AD. This review summarizes the influences of risk factors on peripheral immunity, alongside their functions, highlighting the concept of peripheral and central immunity as an integrated system in AD pathogenesis, which has received scant attention before.

外周免疫在阿尔茨海默病(AD)的发病机制和进展中的意义已被公认。脑浸润的外周免疫成分通过血脑屏障(BBB)转运可能重塑中枢免疫环境。然而,这些成分如何打开AD发生和发展的血脑屏障的机制以及外周免疫和中枢免疫之间的相关性尚未得到充分探索。在此,我们提出了一个假设,即外周免疫作为一个关键因素可以使AD发展。外周中枢免疫细胞串扰与早期AD病理学及相关危险因素有关。受损的血脑屏障允许外周免疫细胞进入中枢免疫系统,剥夺其免疫特权,从而促进AD的发展。本文综述了危险因素对外周免疫的影响及其功能,强调了外周免疫和中枢免疫作为AD发病机制中的一个综合系统的概念,这在以前很少受到关注。
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引用次数: 0
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Cellular immunology
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