Molecular immunology最新文献_第8页

Antibody preparation and immunological analysis of RBD from the SARS-CoV-2 Omicron BF.7 variant SARS-CoV-2 Omicron BF.7变异RBD抗体制备及免疫学分析

IF 3 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecular immunology

Pub Date : 2025-10-07 DOI: 10.1016/j.molimm.2025.09.008

Quansheng Wang , Chenyi Wang , Zhicheng Zhang , Siyu Fan , Ping Lei , Shiguo Liu , Mingzhi Li , Keyi Wang , Yanni Zhang , Lumei Kang , Shiqi Weng , Lingbao Kong , Ting Wang

The SARS-CoV-2 spike protein facilitates target recognition, cellular entry, and viral infection, leading to varying degrees of COVID-19 severity. Amino acid site mutations in the S protein RBD region can enhance the spread and immune evasion of the SARS-CoV-2 Omicron variant. The study aimed to construct a prokaryotic expression vector for the S protein RBD of the SARS-CoV-2 Omicron BF.7 variant strain. Escherichia coli was used to express the RBD protein, and a polyclonal antibody was generated to investigate the immunological functions of the Omicron (BF.7) RBD. Optimization of expression conditions in Escherichia coli was conducted to achieve stable expression of pET-28a-BF.7-RBD, including induced temperature, induced time, and IPTG concentration. Serum antibody titers in RBD-immunized mice reached up to 1: 204800 as determined by indirect enzyme-linked immunosorbent assay. The polyclonal antibody could detect prokaryotic and eukaryotic RBD proteins, as well as commercial RBD proteins, and splenocytes were found to produce high levels of IFN-γ. This study successfully demonstrated the production of a large quantity of RBD protein with strong immunogenicity in E. coli, eliciting robust humoral and cellular immune responses in mice. The generation of high-potency polyclonal antibodies provides valuable insights for further research on the biological functions of the RBD protein, detection of Omicron variants, and vaccine development.

SARS-CoV-2刺突蛋白促进靶标识别、细胞进入和病毒感染，导致不同程度的COVID-19严重程度。S蛋白RBD区氨基酸位点突变可增强SARS-CoV-2 Omicron变体的传播和免疫逃避。本研究旨在构建SARS-CoV-2 Omicron BF.7变异株S蛋白RBD的原核表达载体。利用大肠杆菌表达RBD蛋白，制备多克隆抗体，研究Omicron (BF.7) RBD的免疫学功能。优化pET-28a-BF在大肠杆菌中的表达条件，使其稳定表达。7-RBD，包括诱导温度、诱导时间、IPTG浓度。间接酶联免疫吸附法测定rbd免疫小鼠血清抗体滴度高达1:20 4800。该多克隆抗体可以检测原核和真核RBD蛋白以及商业RBD蛋白，并且发现脾细胞产生高水平的IFN-γ。该研究成功地证明了大肠杆菌产生了大量具有强免疫原性的RBD蛋白，在小鼠中引发了强大的体液和细胞免疫反应。高效多克隆抗体的产生为进一步研究RBD蛋白的生物学功能、检测Omicron变体和疫苗开发提供了有价值的见解。

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引用次数: 0

TNF-α and IFN-γ modulate the evasion of the immune response in primary mediastinal B-cell lymphoma TNF-α和IFN-γ调节原发性纵隔b细胞淋巴瘤的免疫应答逃避。

IF 3 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecular immunology

Pub Date : 2025-10-06 DOI: 10.1016/j.molimm.2025.09.009

Paula Gršković , Valentino Mihalić , Anja Krstulović , Peter Möller , Suzana Hančić , Slavko Gašparov , Petra Korać

Objectives

Primary mediastinal B-cell lymphoma (PMBCL) is an aggressive type of non-Hodgkin lymphoma (NHL) that shares features with diffuse large B-cell lymphoma (DLBCL), but also with classical Hodgkin lymphoma (cHL). PMBCL often contains aberrations of genes involved in the immune response such as cREL and PD-L1, whose expression is also influenced by cytokines TNF-α and IFN-γ.

Methods

In this study, cell lines Farage, U2940, MedB-1 and Karpas1106p were used as PMBCL models and treated with different concentrations of TNF-α and IFN-γ over 24 and 48 h, followed by the quantification of cREL, CXCL10 and PD-L1 expression. Additionally, the expression of TNF-α, IFN-γ, cREL, CXCL10, CXCR3, PD-L1 and PD-1 genes was compared between PMBCL tissue samples and B-cell and T-cell rich zones of non-tumour tonsils.

Results

Prolonged exposure to TNF-α increased cREL expression, while IFN-γ strongly induced CXCL10 expression. The change in the expression of PD-L1 in response to the treatments differed across various cell lines. There was no statistically significant difference in the expression of the target genes between tumour and non-tumour patient tissue samples.

Conclusions

the obtained results suggest that the immune checkpoints in PMBCL cells are affected by both their genetic profile and tumour microenvironment.

目的：原发性纵隔b细胞淋巴瘤（PMBCL）是一种侵袭性非霍奇金淋巴瘤（NHL），其特征与弥漫大b细胞淋巴瘤（DLBCL）相似，但也与经典霍奇金淋巴瘤（cHL）相似。PMBCL通常含有参与免疫反应的基因如cREL和PD-L1的畸变，其表达也受细胞因子TNF-α和IFN-γ的影响。方法：本研究以法拉age、U2940、MedB-1和Karpas1106p细胞系作为PMBCL模型，分别给予不同浓度TNF-α和IFN-γ处理24和48 h，定量测定cREL、CXCL10和PD-L1的表达。此外，比较PMBCL组织样本与非肿瘤扁桃体富含b细胞和t细胞区TNF-α、IFN-γ、cREL、CXCL10、CXCR3、PD-L1和PD-1基因的表达。结果：长时间暴露于TNF-α使cREL表达增加，而IFN-γ强烈诱导CXCL10表达。不同细胞系对PD-L1表达的反应不同。肿瘤和非肿瘤患者组织样本中靶基因的表达无统计学差异。结论：所获得的结果表明PMBCL细胞中的免疫检查点受其遗传谱和肿瘤微环境的影响。

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引用次数: 0

S1PR2-miR-212 feedback loop regulates allergic reactions S1PR2-miR-212反馈回路调节过敏反应。

IF 3 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecular immunology

Pub Date : 2025-10-06 DOI: 10.1016/j.molimm.2025.10.001

Jaewhoon Jeoung, Hyein Jo, Wonho Kim, Dooil Jeoung

We previously reported the anti-allergic effect of rocaglamide-A (roc-A). Molecular docking analysis showed the binding of roc-A to sphingosine-1-phospahe receptor 2 (S1PR2). This led us to hypothesize that S1PR2 might play a role in allergic reactions. Antigen stimulation increased the expression of S1PR2 in rat basophilic leukemia (RBL2H3 cells). Sphingosine-1-phosphate (S1P) increased the expression of S1PR2 in an antigen-independent manner. S1PR2 was necessary for both allergic reactions in vitro and anaphylaxis. Sphingosine prevented the antigen (DNP-HSA) from increasing the expression of S1PR2 and hallmarks of allergic reactions in RBL2H3 cells. Sphingosine also prevented antigen from increasing the level of reactive oxygen species (ROS). Animal model of passive systemic anaphylaxis (PSA) showed the increased expression of CXCL1. CXCL1 was shown to mediate allergic reactions in vitro. TargetScan predicted the binding of miR-212 to the 3 ´ UTR of S1PR2. The downregulation of S1PR2 prevented antigen from increasing the expression of CXCL1 at the transcriptional level. cmiR-212 was found to decrease the expression of S1PR2 in antigen stimulated RBL2H3 cells. miR-212 mimic decreased the luciferase activity associated with 3 ´ UTR of S1PR2. The miR-212 mimic exerted a negative effect on the passive cutaneous anaphylaxis (PCA). The downregulation of S1PR2 increased the expression of miR-212 in antigen stimulated RBL2H3 cells. This suggests that miR-212 and S1PR2 form negative feedback loops to regulate allergic reactions. Our results show that S1PR2-miR-212 negative feedback loop regulates allergic reactions in vitro and in vivo.

我们之前报道了rocaglamide-A （roc-A）的抗过敏作用。分子对接分析显示roc-A与鞘氨醇-1-磷酸受体2 （S1PR2）结合。这使我们假设S1PR2可能在过敏反应中起作用。抗原刺激可增加大鼠嗜碱性白血病（RBL2H3细胞）中S1PR2的表达。鞘氨醇-1-磷酸（S1P）以抗原不依赖的方式增加S1PR2的表达。S1PR2在体外过敏反应和过敏反应中都是必需的。鞘氨醇阻止抗原（DNP-HSA）增加RBL2H3细胞中S1PR2和过敏反应标志的表达。鞘氨醇还能阻止抗原增加活性氧（ROS）的水平。被动全身性过敏反应（PSA）动物模型显示CXCL1表达升高。体外实验显示CXCL1介导过敏反应。TargetScan可以预测miR-212与S1PR2的3 ´ UTR的结合。S1PR2的下调阻止了抗原在转录水平上增加CXCL1的表达。发现cmiR-212在抗原刺激的RBL2H3细胞中降低S1PR2的表达。miR-212 mimic降低了与S1PR2的3 ´ UTR相关的荧光素酶活性。miR-212模拟物对被动皮肤过敏反应（PCA）有负面影响。S1PR2的下调增加了抗原刺激的RBL2H3细胞中miR-212的表达。这表明miR-212和S1PR2形成负反馈回路来调节过敏反应。我们的研究结果表明，S1PR2-miR-212负反馈回路在体外和体内调节过敏反应。

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引用次数: 0

PCBP2 alleviates myocardial infarction by inhibiting cardiomyocyte ferroptosis via the NDUFS1/NRF2 pathway. PCBP2通过NDUFS1/NRF2途径抑制心肌细胞铁下垂，减轻心肌梗死。

IF 3 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecular immunology

Pub Date : 2025-10-01 Epub Date: 2025-08-09 DOI: 10.1016/j.molimm.2025.08.002

Qianrong Zhang, Aiping Jin, Haijuan Cheng, Yuanyuan Zheng, Bing Li

Background: Poly(C) binding protein 2 (PCBP2) was reported to alleviate cardiomyocyte damage, but its molecular mechanism remains unclear. The current study aimed to investigate the role and potential mechanism of PCBP2 in progression of MI.

Methods: An in vivo MI model was established by ligation of the left anterior descending (LAD) branch in mice. PCBP2 expression was detected in Normal and MI groups. H9C2 cells were treated with OGD for 0, 2, 4, and 6 h to screen for optimal time to establish MI model in vitro. H9C2 cells were transfected with pcDNA-PCBP2, and the effect of PCBP2 overexpression on OGD-induced oxidative stress, inflammation and ferroptosis was evaluated. Subsequently, the interaction of PCBP2 with NDUFS1 mRNA was predicted by the Starbase database and verified by RNA-immunoprecipitation (RIP) and RNA-protein pull-down assay. Next, a series of reversal experiments were performed to verify the regulation of PCBP2 on NDUFS1 expression. Then, pcDNA-NDUFS1 was transfected into H9C2 and MIND4-17 (NRF2 protein activator) treated for reversal experiments to assess the effect of NDUFS1 on NRF2-mediated ferroptosis. Finally, LV-PCBP2 and LV-NDUFS1 lentiviral vectors were intrapericardially injected into MI mice, and the role of PCBP2 and NDUFS1 in the progression of MI was verified in vivo.

Results: PCBP2 was downregulated in MI model and OGD-induced H9C2 cells. PCBP2 improved cell proliferation and inhibited oxidative stress, inflammation and ferroptosis in OGD-incubated H9C2 cells. PCBP2 bound with NDUFS1 mRNA and promoted NDUFS1 expression in H9C2 cells, which promoted NRF2 activation by enhancing NRF2 nuclear translocation and inhibited NRF2-mediated ferroptosis. Finally, administration of LV-PCBP2 and LV-NDUFS1 alleviated myocardial tissue injury and MI infarct in mice through suppressing cardiomyocyte ferroptosis and inflammation.

Conclusion: Our results suggested that PCBP2 alleviated MI by inhibiting cardiomyocyte ferroptosis through interacting with NDUFS1 mRNA and activating NRF2-Keap1 pathway.

背景：聚(C)结合蛋白2 （PCBP2）有减轻心肌细胞损伤的报道，但其分子机制尚不清楚。本研究旨在探讨PCBP2在心肌梗死进展中的作用及其可能的机制。方法：采用结扎左前降支的方法建立小鼠心肌梗死模型。正常组和心肌梗死组均检测到PCBP2的表达。OGD作用H9C2细胞0、2、4、6 h，筛选体外建立心肌梗死模型的最佳时间。用pcDNA-PCBP2转染H9C2细胞，观察PCBP2过表达对ogd诱导的氧化应激、炎症和铁凋亡的影响。随后，通过Starbase数据库预测PCBP2与NDUFS1 mRNA的相互作用，并通过rna免疫沉淀（RIP）和rna蛋白拉下实验进行验证。接下来，我们通过一系列的逆转实验来验证PCBP2对NDUFS1表达的调控作用。然后，将pcDNA-NDUFS1转染到H9C2和处理过的MIND4-17 （NRF2蛋白激活剂）中进行逆转实验，以评估NDUFS1对NRF2介导的铁下沉的影响。最后，通过心包内注射LV-PCBP2和LV-NDUFS1慢病毒载体，在体内验证PCBP2和NDUFS1在心肌梗死进展中的作用。结果：心肌梗死模型和ogd诱导的H9C2细胞中PCBP2表达下调。PCBP2促进ogd培养的H9C2细胞增殖，抑制氧化应激、炎症和铁下垂。PCBP2结合NDUFS1 mRNA，促进NDUFS1在H9C2细胞中的表达，通过增强NRF2核易位促进NRF2活化，抑制NRF2介导的铁凋亡。最后，LV-PCBP2和LV-NDUFS1通过抑制心肌细胞下垂和炎症减轻小鼠心肌组织损伤和心肌梗死。结论：PCBP2通过与NDUFS1 mRNA相互作用，激活NRF2-Keap1通路，抑制心肌细胞铁下沉，从而减轻心肌梗死。

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引用次数: 0

Protocatechuic aldehyde promotes diabetic wound healing by enhancing angiogenesis via H3K18 lactylation-mediated Acvr1c expression 原儿茶醛通过H3K18乳酸化介导的Acvr1c表达促进血管生成，从而促进糖尿病伤口愈合。

IF 3 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecular immunology

Pub Date : 2025-09-30 DOI: 10.1016/j.molimm.2025.09.002

Weijing Fan , Yang You , Yin Qu, Guobin Liu

Delayed wound recovery is a major health issue affecting people with diabetes. Histone lactylation is involved in tissue repair. However, it is not clear whether protocatechuic aldehyde (PCA) promotes diabetic wound healing through histone lactylation. In this study, a diabetic wound mouse model was constructed to delve into the role of PCA in vivo. Chromatin immunoprecipitation sequencing (ChIP-seq) was used to determine genes affected by H3K18 lactylation (H3K18la) under PCA treatment. The effects and mechanisms of PCA on histone lactylation and angiogenesis were investigated through cellular experiments. We found that PCA accelerated wound healing and angiogenesis in diabetic mice, and significantly reduced the inflammatory response in wound tissues. Lactate and H3K18la levels were augmented in the model group in comparison with the control group, however, PCA treatment remarkably reversed their levels. ChIP-seq analysis revealed a significant enrichment of H3K18la at the Acvr1c locus, and this histone modification was downregulated by PCA treatment. PCA remarkably enhanced Acvr1c expression through H3K18la in HUVECs. Moreover, PCA treatment markedly elevated cell viability, migration and tube formation in comparison with the control group. However, this effect was counteracted by Acvr1c knockdown. In conclusion, PCA promoted HUVEC angiogenesis by increasing H3K18la-mediated Acvr1c expression, thereby promoting diabetic wound healing. This could offer a new treatment approach to enhance the effectiveness of healing diabetic wounds.

伤口恢复延迟是影响糖尿病患者的主要健康问题。组蛋白乳酸化参与组织修复。然而，原儿茶醛（PCA）是否通过组蛋白乳酸化促进糖尿病伤口愈合尚不清楚。本研究通过构建糖尿病创面小鼠模型，探讨PCA在体内的作用。采用染色质免疫沉淀测序（ChIP-seq）检测PCA处理下受H3K18乳酸化（H3K18la）影响的基因。通过细胞实验研究了PCA对组蛋白乳酸化和血管生成的影响及其机制。我们发现，PCA加速了糖尿病小鼠的伤口愈合和血管生成，并显著降低了伤口组织的炎症反应。与对照组相比，模型组乳酸和H3K18la水平升高，但PCA处理显著逆转了它们的水平。ChIP-seq分析显示，H3K18la在Acvr1c位点显著富集，这种组蛋白修饰在PCA处理下被下调。PCA通过H3K18la显著增强huvec中Acvr1c的表达。此外，与对照组相比，PCA治疗显著提高了细胞活力、迁移和管形成。然而，这种作用被Acvr1c敲低所抵消。综上所述，PCA通过增加h3k18la介导的Acvr1c表达促进HUVEC血管生成，从而促进糖尿病创面愈合。这可能为提高糖尿病伤口愈合的有效性提供一种新的治疗方法。

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引用次数: 0

The mechanism of SMAD4/ERK pathway in regulating Th17/Treg cell differentiation leading to olfactory dysfunction in chronic rhinosinusitis SMAD4/ERK通路调控Th17/Treg细胞分化导致慢性鼻窦炎嗅觉功能障碍的机制

IF 3 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecular immunology

Pub Date : 2025-09-25 DOI: 10.1016/j.molimm.2025.09.006

Shouming Cao , Yan Niu , Jinmei Ning , Nannan Wen , Rui Chen , Haiying Wu

Background

Chronic rhinosinusitis (CRS) is characterized by a high recurrence rate within five years post-surgery, posing a persistent challenge for otolaryngologists globally. Recent research has underscored the pivotal role of the Th17/Treg cell balance in the pathogenesis of CRS. This study aims to investigate the alterations in the Th17/Treg cell balance in CRS and elucidate the underlying molecular mechanisms.

Methods

CRS model was established to assess the levels of inflammatory cytokines, olfactory marker protein expression, SMAD4 expression, and ERK1/2 phosphorylation. We then overexpressed SMAD4 or treated CRS mice with ERK1/2 inhibitors, measuring the impact on Th17/Treg marker expression. Moreover, the influence of the SMAD4/ERK signaling axis on the Th17/Treg balance within the CD4 + T cell population was investigated.

Results

CRS mice exhibited significantly reduced olfactory marker protein and SMAD4 expression, alongside increased ERK1/2 phosphorylation. Histological analysis revealed an increased infiltration of eosinophils. Of particular note, the expression of Treg markers was markedly decreased, while Th17 marker expression exhibited a corresponding increase, suggesting a potential shift in the Th17/Treg balance. Interventions involving SMAD4 overexpression or ERK1/2 inhibition led to a reduction in eosinophil infiltration and successfully reversed the aberrant expression patterns of the aforementioned markers. Furthermore, SMAD4 knockdown resulted in a decreased proportion of Treg cells and an increased proportion of Th17 cells. This alteration in the Th17/Treg balance was effectively counteracted by ERK inhibitor.

Conclusions

The deletion of SMAD4 regulates the differentiation of Th17/Treg cells via ERK1/2 phosphorylation, thereby exacerbating the olfactory dysfunction of CRS.

慢性鼻窦炎（CRS）的特点是术后5年内复发率高，对全球耳鼻喉科医生构成了持续的挑战。最近的研究强调了Th17/Treg细胞平衡在CRS发病机制中的关键作用。本研究旨在探讨CRS中Th17/Treg细胞平衡的改变，并阐明其分子机制。方法建立scrs模型，评估炎症因子、嗅觉标志蛋白表达、SMAD4表达和ERK1/2磷酸化水平。然后，我们过表达SMAD4或用ERK1/2抑制剂治疗CRS小鼠，测量对Th17/Treg标记物表达的影响。此外，我们还研究了SMAD4/ERK信号轴对CD4 + T细胞群中Th17/Treg平衡的影响。结果scrs小鼠嗅觉标记蛋白和SMAD4表达显著降低，ERK1/2磷酸化水平升高。组织学分析显示嗜酸性粒细胞浸润增加。特别值得注意的是，Treg标记物的表达明显下降，而Th17标记物的表达则相应增加，这表明Th17/Treg平衡可能发生了变化。涉及SMAD4过表达或ERK1/2抑制的干预导致嗜酸性粒细胞浸润减少，并成功逆转上述标记物的异常表达模式。此外，SMAD4敲除导致Treg细胞比例下降，Th17细胞比例增加。这种Th17/Treg平衡的改变被ERK抑制剂有效地抵消了。结论SMAD4缺失通过ERK1/2磷酸化调控Th17/Treg细胞的分化，从而加重CRS的嗅觉功能障碍。

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引用次数: 0

Therapeutic targeting of neuroinflammation in sphingolipidosis 鞘脂病神经炎症的靶向治疗

IF 3 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecular immunology

Pub Date : 2025-09-23 DOI: 10.1016/j.molimm.2025.09.005

Ebru Ada , Volkan Seyrantepe

Lysosomal storage diseases (LSDs) are a class of hereditary metabolic disorders primarily caused by lysosomal enzyme defects, leading to the accumulation of undegraded substrates. Sphingolipidoses, a subset of LSDs, are primarily associated with profound involvement of the central nervous system (CNS), characterized by progressive neurodegeneration due to massive sphingolipid accumulation. A common pathological feature among many CNS-involved LSDs is the early activation of microglia and astrocytes, which often precedes and predicts regions of subsequent neuronal loss. The extent to which neuroinflammation disrupts CNS homeostasis appears to be determined by its onset, magnitude, and duration. Although neuroinflammatory processes are increasingly recognized as critical contributors to disease progression in sphingolipidoses, the molecular mechanisms underlying glial activation and the initiation of inflammatory cascades remain incompletely understood. Therefore, mouse models of sphingolipidoses have been instrumental in elucidating these pathogenic processes and provide valuable platforms for evaluating therapeutic strategies. This review critically examines the role of neuroinflammation in sphingolipidoses, summarizes insights derived from pre-clinical models, and discusses the therapeutic potential of anti-inflammatory interventions to mitigate CNS pathology and improve clinical outcomes.

溶酶体贮积病（lsd）是一类主要由溶酶体酶缺陷引起的遗传性代谢疾病，导致未降解底物的积累。鞘脂病是lsd的一个亚型，主要与中枢神经系统（CNS）的深度受累有关，其特征是由于大量鞘脂积累导致的进行性神经退行性变。在许多涉及中枢神经系统的lsd中，一个共同的病理特征是小胶质细胞和星形胶质细胞的早期激活，这通常先于并预测随后的神经元丢失区域。神经炎症破坏中枢神经系统稳态的程度似乎取决于其发病、程度和持续时间。尽管神经炎症过程越来越多地被认为是鞘脂病疾病进展的关键因素，但神经胶质激活和炎症级联反应启动的分子机制仍不完全清楚。因此，小鼠鞘脂病模型有助于阐明这些致病过程，并为评估治疗策略提供有价值的平台。本文综述了神经炎症在鞘脂病中的作用，总结了从临床前模型中得到的见解，并讨论了抗炎干预减轻中枢神经系统病理和改善临床结果的治疗潜力。

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引用次数: 0

Hypocontractile airway smooth muscle phenotype exhibits enhanced β2 laminin chain expression in lung allergy model 肺变态反应模型中，低收缩气道平滑肌表型β2层粘连蛋白链表达增强

IF 3 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecular immunology

Pub Date : 2025-09-23 DOI: 10.1016/j.molimm.2025.09.003

Ivonne Pacheco-Alba , Blanca Bazán-Perkins

Sensitization with ovalbumin (OVA) in guinea pigs to induce anti-OVA IgE generates various allergic response phenotypes. One phenotype, characterized by the absence of bronchial obstruction and airway hyperresponsiveness in response to chronic antigen challenge, is termed non-responding (NR) and exhibits high IFN-γ levels. The Th1 cytokine profile is linked with high laminin β2 expression. This study evaluated laminin β2 expression in the chronic NR phenotype. Guinea pigs were sensitized and challenged with OVA three times (acute) or twelve times (chronic). Guinea pigs that responded to all challenges formed the asthma model phenotype. Controls were sensitized and challenged with saline. Immunohistochemistry was used to observe laminin β2 and its receptor, the α6 integrin subunit, in bronchial and arterial intrapulmonary smooth muscles. Only chronic NR guinea pigs showed increased laminin β2 expression in these muscles, while it remained similar in other groups. The α6 integrin subunit significantly increased in the acute and chronic asthma models, chronic controls, and NR guinea pigs in bronchial smooth muscle. In arterial intrapulmonary smooth muscle, the α6 integrin subunit increased in acute NR and chronic asthma model guinea pigs. The expression of laminin β2 in bronchial and arterial intrapulmonary smooth muscles correlates with α6 integrin subunit levels, and higher levels of laminin β2 were significantly related to reduced antigen-induced bronchial obstruction and reactivity to histamine. The expression of these proteins does not affect the proliferation of pulmonary blood vessels. Laminin β2 chain overexpression is likely involved in the chronic containment of the obstructive allergic response.

用卵清蛋白（OVA）致敏豚鼠诱导抗OVA IgE产生各种过敏反应表型。一种表型，其特征是对慢性抗原攻击没有支气管阻塞和气道高反应性，被称为无反应（NR），并表现出高IFN-γ水平。Th1细胞因子谱与层粘连蛋白β2的高表达有关。本研究评估了层粘连蛋白β2在慢性NR表型中的表达。用OVA致敏和攻毒豚鼠3次（急性）或12次（慢性）。对所有挑战都有反应的豚鼠形成了哮喘模型表型。对照组致敏并给予生理盐水刺激。采用免疫组化方法观察层粘连蛋白β2及其受体α6整合素亚基在支气管和动脉肺内平滑肌中的表达。只有慢性NR豚鼠在这些肌肉中表现出层粘连蛋白β2的表达增加，而在其他组中保持相似。α6整合素亚基在急、慢性哮喘模型、慢性对照和NR豚鼠支气管平滑肌中显著升高。急性NR和慢性哮喘模型豚鼠动脉肺内平滑肌α6整合素亚基升高。层粘连蛋白β2在支气管和动脉肺内平滑肌中的表达与α6整合素亚基水平相关，较高的层粘连蛋白β2水平与减少抗原诱导的支气管阻塞和组胺反应性显著相关。这些蛋白的表达不影响肺血管的增殖。层粘连蛋白β2链过表达可能参与了阻塞性过敏反应的慢性抑制。

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引用次数: 0

Monochromatic green light-mediated melatonin promotes cecal barrier function in broilers 单色绿光介导的褪黑素促进肉鸡盲肠屏障功能

IF 3 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecular immunology

Pub Date : 2025-09-19 DOI: 10.1016/j.molimm.2025.09.004

Tao Quan, Ran Li, Yaoxing Chen, Ting Gao

Light plays a crucial role as an environmental factor, greatly affecting chick behavior, production performance and health. Melatonin, an essential marker of photoelectric signaling, plays a role in regulating various physiological functions in broilers, such as gut health. However, whether monochromatic light can mediate melatonin secretion to regulate intestinal function and its regulatory mechanism are not known. In the present study, we showed that monochromatic green light significantly enhanced the mucosal barrier function of the broiler cecum, including the up-regulation of goblet cells and their secreted MUC2 content, tight junction protein expression and enterocyte proliferative viability. However, when the pineal gland was removed, accompanied by a decrease in melatonin content, the green light advantage disappeared and the intestinal mucosal barrier function was severely impaired. Mechanistically, we found that monochromatic green light promotes melatonin secretion, which enters the intestine to bind Mel1a receptors located on macrophage membranes in cecum, inhibits its downstream TLR4/ERK/JNK/NF-κB signaling pathway, promotes M2-type macrophage polarization, reduces intestinal inflammation levels while up-regulating intestinal antioxidant levels, and ultimately strengthens the cecum mucosal barrier function. Our findings provide new theoretical support for the future use of melatonin during intestinal development, as well as theoretical guidance for the proper application of artificial lighting in the modern chicken industry to improve chicken's intestinal health.

光作为一种环境因子，对雏鸡的行为、生产性能和健康有着重要的影响。褪黑素是一种重要的光电信号标志物，在调节肉鸡肠道健康等多种生理功能中发挥重要作用。然而，单色光是否能介导褪黑激素分泌调节肠道功能及其调节机制尚不清楚。在本研究中，我们发现单色绿光显著增强了肉鸡盲肠粘膜屏障功能，包括上调杯状细胞及其分泌MUC2含量、上调紧密连接蛋白表达和肠细胞增殖活力。然而，当松果体被切除时，伴随着褪黑激素含量的减少，绿光优势消失，肠黏膜屏障功能严重受损。在机制上，我们发现单色绿光促进褪黑激素分泌，褪黑激素进入肠道结合位于盲肠巨噬细胞膜上的Mel1a受体，抑制其下游TLR4/ERK/JNK/NF-κB信号通路，促进m2型巨噬细胞极化，降低肠道炎症水平，上调肠道抗氧化水平，最终增强盲肠黏膜屏障功能。我们的研究结果为未来肠道发育过程中褪黑素的使用提供了新的理论支持，也为现代养鸡业中合理应用人工照明改善鸡肠道健康提供了理论指导。

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引用次数: 0

Characterization of the heterogeneity in oxidative stress and transcriptional programs within the in vivo microenvironment of ulcerative colitis 溃疡性结肠炎体内微环境中氧化应激和转录程序异质性的表征

IF 3 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecular immunology

Pub Date : 2025-09-09 DOI: 10.1016/j.molimm.2025.08.017

Yongwei Zhuang , Ran Ye , Jingyu Chen , Gefei Chen , Luyi Chen , Yabi Zhu , Shufang Ye , Yangyang Liu

Objective

Oxidative stress exerts an essential role in the pathogenesis of ulcerative colitis (UC). This study aims to unveil the heterogeneity in oxidative stress among immune cell subpopulations in UC.

Methods

Human colon epithelial cells were exposed to 100 ng/mL LPS to stimulate UC, which were administrated with antioxidants 500 mM butylated hydroxyanisole or 20 μM N-acetylcysteine. A single-cell atlas was constructed across UC, and heterogeneous cell subpopulations were evaluated at single-cell and bulk levels.

Results

Activation of oxidative stress and inflammatory response, enhanced migration capacity, and impaired tight junction were observed in LPS-induced UC cell models, which were ameliorated by antioxidants. Five cell types: plasma cells, T cells, myeloid cells, and B cells were clustered across UC and control gut biopsies, which were tightly interacted. Myeloid cells were sub-clustered into conventional dendritic cells, M1 macrophages, IL23R⁺ myeloid cells, mast cells, and follicular dendritic cells; T cells were sub-clustered into Th17, CD4⁺ naïve T cells, CD8⁺ cytotoxic T cells, CD4⁺ exhausted T cells, CD8⁺ memory T cells, Tregs, and Th1. The heterogeneous myeloid and T cells was confirmed at the single-cell and bulk levels. The activity of oxidative stress was heterogeneous among diverse myeloid cell or T cell subpopulations, with the strongest activity in M1 macrophages and CD4⁺ exhausted T cells, respectively. It was also found the specific transcriptional programs of M1 macrophages and CD8⁺ cytotoxic T cells.

Conclusion

Overall, our findings unveil the heterogeneity in oxidative stress and transcriptional programs among diverse myeloid and T cell subpopulations in UC.

目的氧化应激在溃疡性结肠炎（UC）的发病机制中发挥重要作用。本研究旨在揭示UC免疫细胞亚群中氧化应激的异质性。方法将人结肠上皮细胞暴露于100 ng/mL LPS刺激UC，并给予500 mM丁基羟基异黄酮或20 μM n -乙酰半胱氨酸抗氧化剂。在UC中构建单细胞图谱，并在单细胞和整体水平上评估异质细胞亚群。结果在lps诱导的UC细胞模型中观察到氧化应激和炎症反应激活，迁移能力增强，紧密连接受损，抗氧化剂改善。五种细胞类型：浆细胞、T细胞、骨髓细胞和B细胞聚集在UC和对照肠道活检中，它们紧密相互作用。髓样细胞亚簇分为常规树突状细胞、M1巨噬细胞、IL23R+髓样细胞、肥大细胞和滤泡树突状细胞；T细胞亚簇分为Th17、CD4+ naïve T细胞、CD8+细胞毒性T细胞、CD4+耗竭T细胞、CD8+记忆T细胞、Tregs和Th1。在单细胞和整体水平上证实了骨髓细胞和T细胞的异质性。氧化应激的活性在不同的骨髓细胞或T细胞亚群中是不均匀的，其中M1巨噬细胞和CD4+耗竭T细胞的活性最强。我们还发现了M1巨噬细胞和CD8+细胞毒性T细胞的特异性转录程序。总之，我们的发现揭示了UC不同髓细胞和T细胞亚群中氧化应激和转录程序的异质性。

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引用次数: 0