Immunity, Inflammation and Disease最新文献

Predicting Role of Interleukin-33 in Determining the Development and Severity of Atopic Dermatitis 白细胞介素-33在确定特应性皮炎发展和严重程度中的预测作用

IF 2.7 4区医学 Q3 IMMUNOLOGY

Immunity, Inflammation and Disease

Pub Date : 2026-02-08 DOI: 10.1002/iid3.70351

Ali-reza Ghasemiyeh, Marzieh Heidarzadeh Arani, Fatemeh Riazian, Ali Aghajani, Mohammad Javad Azadchehr, Hossein Motedayyen

Introduction

Atopic dermatitis (AD), also referred to as atopic eczema, is one of the most common immunological disorders in children. Previous studies have suggested potential roles of interleukin-33 (IL-33) in the onset and progression of AD. This study investigated whether serum IL-33 levels in children with AD are associated with disease severity, immunoglobulin E (IgE) sensitization to food or environmental allergens, and serum IgE concentration.

Methods

The study included 62 children with newly diagnosed AD and 30 age-matched healthy controls. Following an interview and confirmation of disease severity, 3mL of venous blood was collected from each participant. Sensitization to allergens was assessed using a skin prick test. Serum IL-33 (ng/L) and IgE (IU/mL) levels were measured using enzyme-linked immunosorbent assay (ELISA).

Results

Among the 62 children with AD, 51 (82.3%) were sensitized to food allergens, whereas 11 (17.7%) were sensitized to environmental allergens. Most patients (75.8%) had mild AD. Serum IL-33 and IgE levels were significantly elevated in patients compared with healthy controls. Both IL-33 and IgE concentrations were significantly associated with moderate AD. However, IL-33 levels were not correlated with age, gender, or allergen type. Receiver operating characteristic (ROC) analysis revealed that IgE levels demonstrated moderate diagnostic performance for AD (AUCc0.758), while IL-33 showed weaker diagnostic value (AUC = 0.678). For predicting disease severity, IL-33 exhibited strong performance, with the highest sensitivity (85.71%) and maximum specificity (70.21%) at a cut-off of 331.32 ng/L (AUC = 0.862). In contrast, IgE was not a reliable predictor of AD severity.

Conclusion

Serum IL-33 levels are significantly correlated with AD severity and may serve as a predictive biomarker, whereas IgE shows limited utility for severity assessment. Further studies are warranted to validate the clinical applicability of IL-33 in AD management.

特应性皮炎（AD），又称特应性湿疹，是儿童最常见的免疫系统疾病之一。先前的研究表明，白细胞介素-33 （IL-33）在AD的发生和发展中可能起作用。本研究探讨AD患儿血清IL-33水平是否与疾病严重程度、免疫球蛋白E （IgE）对食物或环境过敏原的致敏性以及血清IgE浓度相关。方法研究对象为62例新诊断的AD患儿和30例年龄匹配的健康对照。在访谈和确认疾病严重程度后，从每位参与者收集3mL静脉血。使用皮肤点刺试验评估对过敏原的致敏性。采用酶联免疫吸附法（ELISA）检测血清IL-33 （ng/L）和IgE （IU/mL）水平。结果62例AD患儿中，食物过敏原致敏51例（82.3%），环境过敏原致敏11例（17.7%）。大多数患者（75.8%）为轻度AD。与健康对照组相比，患者血清IL-33和IgE水平显著升高。IL-33和IgE浓度均与中度AD显著相关。然而，IL-33水平与年龄、性别或过敏原类型无关。受试者工作特征（ROC）分析显示，IgE水平对AD的诊断价值中等（AUC = 0.758）， IL-33的诊断价值较弱（AUC = 0.678）。在预测疾病严重程度方面，IL-33表现出很强的性能，灵敏度最高（85.71%），特异性最高（70.21%），截止值为331.32 ng/L （AUC = 0.862）。相反，IgE并不是AD严重程度的可靠预测因子。结论血清IL-33水平与AD严重程度显著相关，可作为AD严重程度的预测性生物标志物，而IgE在AD严重程度评估中的应用有限。需要进一步研究来验证IL-33在AD治疗中的临床适用性。

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引用次数: 0

WTAP Contributes to Periodontitis Pathogenesis by Promoting PDLSC Senescence and Impairing Osteogenic Differentiation via m6A-Dependent Regulation of TP53BP1 WTAP通过m6a依赖性调控TP53BP1，促进PDLSC衰老，损害成骨分化，参与牙周炎发病。

IF 2.7 4区医学 Q3 IMMUNOLOGY

Immunity, Inflammation and Disease

Pub Date : 2026-02-05 DOI: 10.1002/iid3.70335

Menglin Xiong, Tingting Wang, Yuan Liu

Background

Periodontitis, a chronic inflammatory disease, represents the primary cause of tooth loss in Chinese adults. Wilms tumor 1-associating protein (WTAP) is a key component of the N6-methyladenosine (m6A) methyltransferase complex, and has an unclear role in periodontitis pathogenesis, particularly concerning its regulatory functions in periodontal ligament stem cells (PDLSCs).

Methods

The target gene was identified through the GES260558 dataset and Genecards database. Gene expression was measured using reverse transcription-quantitative PCR (RT-qPCR) and western blot. Periodontitis-derived PDLSCs (P-PDLSCs) were isolated and identified by alkaline phosphatase (ALP) staining, oil red O staining, and flow cytometry. Malondialdehyde (MDA), superoxide dismutase (SOD), and reactive oxygen species (ROS) levels, γ-H2AX and SA-β-gal positive cells, and the expression of p53 and p16 were applied to reflect oxidative stress and cell senescence. Osteogenic differentiation was assessed by ALP activity, alizarin red S (ARS) staining, and related gene expression. The m6A-dependent regulation of tumor protein p53 binding protein 1 (TP53BP1) mRNA by WTAP was confirmed using methylated RNA immunoprecipitation (MeRIP), RNA immunoprecipitation (RIP), and Actinomycin D (Act D) assays.

Results

WTAP was identified as a candidate gene that was upregulated in periodontitis gingival tissues. Isolated P-PDLSCs retained normal multilineage differentiation potential. WTAP knockdown significantly reduced senescence and oxidative stress in P-PDLSCs while enhancing osteogenic differentiation. Mechanistically, WTAP mediated the m6A modification of TP53BP1 mRNA, and the effects of WTAP on P-PDLSC senescence, oxidative stress, and osteogenic differentiation were dependent on TP53BP1.

Conclusion

The WTAP/TP53BP1 axis impairs periodontal tissue regeneration by promoting P-PDLSC senescence and suppressing osteogenic differentiation in an m6A-dependent manner, revealing a new cellular-level target for treating periodontitis.

背景：牙周炎是一种慢性炎症性疾病，是中国成年人牙齿脱落的主要原因。Wilms肿瘤1相关蛋白（WTAP）是n6 -甲基腺苷（m6A）甲基转移酶复合物的关键组成部分，在牙周炎发病机制中的作用尚不清楚，特别是其在牙周韧带干细胞（PDLSCs）中的调节功能。方法：通过GES260558数据集和Genecards数据库对目的基因进行鉴定。采用逆转录定量PCR （RT-qPCR）和western blot检测基因表达。采用碱性磷酸酶（ALP）染色、油红O染色和流式细胞术分离鉴定牙周炎源性PDLSCs （P-PDLSCs）。丙二醛（MDA）、超氧化物歧化酶（SOD）和活性氧（ROS）水平、γ-H2AX和SA-β-gal阳性细胞以及p53和p16的表达反映氧化应激和细胞衰老情况。通过ALP活性、茜素红S （ARS）染色及相关基因表达评估成骨分化。通过甲基化RNA免疫沉淀（MeRIP）、RNA免疫沉淀（RIP）和放射线霉素D （Act D）检测，证实了WTAP对肿瘤蛋白p53结合蛋白1 (TP53BP1) mRNA的m6a依赖性调控。结果：WTAP被确定为牙周炎牙龈组织中表达上调的候选基因。分离的P-PDLSCs保留了正常的多系分化潜能。WTAP敲除显著降低P-PDLSCs的衰老和氧化应激，同时增强成骨分化。机制上，WTAP介导TP53BP1 mRNA的m6A修饰，WTAP对P-PDLSC衰老、氧化应激和成骨分化的影响依赖于TP53BP1。结论：WTAP/TP53BP1轴通过m6a依赖的方式促进P-PDLSC衰老和抑制成骨分化，从而损害牙周组织再生，揭示了治疗牙周炎的一个新的细胞水平靶点。

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引用次数: 0

Reducing Neuroinflammation via Inhibition of Fibrinogen Deposition and Microglial Activation as an Underlying Mechanism of Paning I Decoction in Ameliorating Parkinson's Disease Symptoms 通过抑制纤维蛋白原沉积和小胶质细胞活化减轻神经炎症：潘宁1汤改善帕金森病症状的潜在机制

IF 2.7 4区医学 Q3 IMMUNOLOGY

Immunity, Inflammation and Disease

Pub Date : 2026-02-05 DOI: 10.1002/iid3.70310

Yan-Jun Chen, Jing-Wen Chen, Ming-Rong Xie, Rui-Zhen Wang, Yu-Ling Wan, Jie Zeng, Bing-Wu Zhong, Sheng-Qiang Zhou, Fang Liu

Background

Parkinson's disease (PD) is a major neurodegenerative disorder. Some patients show limited response to standard therapies, driving the need for new complementary treatments. Paning I decoction (PNID), a traditional herbal formula, has shown the potential to alleviate PD symptoms, but its exact mechanisms remain unclear.

Methods

We tested PNID in a mouse model of PD induced by a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Mice received different PNID doses to evaluate symptom alleviation. We used behavioral tests and laboratory analyses to study brain changes, including neuron damage assessment, dopamine and tyrosine hydroxylase (TH) measurements, blood–brain barrier (BBB) integrity and microglia evaluation, and inflammatory marker analysis.

Results

PNID treatment alleviated PD symptoms in a dose-dependent manner. High-dose PNID performed similarly to Madopar. Neuron protection: increased dopamine and TH expression. BBB repair: less leakage and fibrinogen accumulation. Regulation of polarization: shifted microglia from M1 to M2 states. Inflammation control: lowered pro-inflammatory factors (IL-6, IL-1β, and TNF-α) while increasing anti-inflammatory factors (IFN-β, IL-10, and IL-4).

Conclusions

PNID may serve as a promising complementary therapy for PD. Benefits may come from the repair of the BBB, reduction of fibrinogen deposition, and decline in neuroinflammation by modulating microglial polarization.

背景：帕金森病（PD）是一种主要的神经退行性疾病。一些患者对标准疗法的反应有限，因此需要新的补充疗法。panning I汤（PNID）是一种传统的草药配方，已显示出缓解PD症状的潜力，但其确切机制尚不清楚。方法：在1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）诱导的PD小鼠模型中检测PNID。小鼠接受不同剂量的PNID来评估症状缓解。我们使用行为测试和实验室分析来研究大脑的变化，包括神经元损伤评估、多巴胺和酪氨酸羟化酶（TH）测量、血脑屏障（BBB）完整性和小胶质细胞评估以及炎症标志物分析。结果：PNID治疗对PD症状的缓解呈剂量依赖性。高剂量PNID的效果与美多帕相似。神经元保护：多巴胺和TH表达增加。血脑屏障修复：减少渗漏和纤维蛋白原积聚。极化调节：将小胶质细胞从M1状态转移到M2状态。炎症控制：降低促炎因子（IL-6、IL-1β、TNF-α），增加抗炎因子（IFN-β、IL-10、IL-4）。结论：PNID可作为PD的补充治疗。益处可能来自于血脑屏障的修复，纤维蛋白原沉积的减少，以及通过调节小胶质细胞极化来减轻神经炎症。

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引用次数: 0

NLRP3-Caspase-1 Axis in Human Adipose Tissue Crown-Like Structures: A Potential Mediator of Inflammation and the Effects of Bariatric Surgery 人类脂肪组织冠状结构中的NLRP3-Caspase-1轴：炎症的潜在介质和减肥手术的影响

IF 2.7 4区医学 Q3 IMMUNOLOGY

Immunity, Inflammation and Disease

Pub Date : 2026-02-05 DOI: 10.1002/iid3.70312

Ville A. Palomäki, Juha P. Väyrynen, Vesa Koivukangas, Sanna Meriläinen, Tuomo J. Karttunen, Petri Lehenkari

Background

Obesity-related comorbidities, such as type 2 diabetes, are associated with chronic inflammation mediated by macrophages. This inflammation is characterized by the accumulation of macrophages in crown-like structures (CLS) surrounding dead adipocytes within adipose tissue. In a recent study, we reported a significant reduction in CLS-associated macrophages following bariatric surgery. The NLRP3 inflammasome and its downstream effector, Caspase-1, are well-established mediators of metabolic dysfunction and inflammation in obesity.

Methods

Immunohistochemical single- and multiplex staining of subcutaneous adipose tissue (SAT) samples from patients with obesity was performed to characterize the detailed distribution of NLRP3 and Caspase-1. The samples were collected during gastric bypass surgery and at a 1-year follow-up.

Results

Both NLRP3 and Caspase-1 were expressed by CD68-positive macrophages in SAT including both single macrophages and those forming CLS. A reduction in the total number of SAT macrophages expressing these proteins was detected following gastric bypass. Furthermore, NLRP3 and Caspse-1 were observed in the endothelium of vascular structures.

Conclusions

Our findings demonstrate that both CLS-forming and single cell macrophage populations in human adipose tissue express NLRP3 and Caspase-1. The study highlights the significance of the NLRP3 inflammasome macrophages in the pathogenesis of adipose tissue inflammation in obesity. The previously reported abundance of CLS in untreated obesity and their reduction after bariatric surgery suggest that the NLRP3-Caspase-1 axis within CLS may serve as an important mediator of the beneficial metabolic effects associated with bariatric surgery.

背景：肥胖相关的合并症，如2型糖尿病，与巨噬细胞介导的慢性炎症有关。这种炎症的特征是巨噬细胞在脂肪组织内死亡脂肪细胞周围的冠状结构（CLS）中积聚。在最近的一项研究中，我们报道了减肥手术后cls相关巨噬细胞的显著减少。NLRP3炎症小体及其下游效应物Caspase-1是肥胖症代谢功能障碍和炎症的公认介质。方法：对肥胖患者皮下脂肪组织（SAT）样本进行免疫组织化学单次和多重染色，以表征NLRP3和Caspase-1的详细分布。样本在胃旁路手术期间和1年随访期间收集。结果：NLRP3和Caspase-1均通过cd68阳性的巨噬细胞在SAT中表达，包括单核巨噬细胞和形成CLS的巨噬细胞。胃旁路治疗后，检测到表达这些蛋白的SAT巨噬细胞总数减少。此外，在血管结构的内皮中也观察到NLRP3和Caspse-1的表达。结论：我们的研究结果表明，人脂肪组织中cls形成和单细胞巨噬细胞群体均表达NLRP3和Caspase-1。本研究强调了NLRP3炎性小体巨噬细胞在肥胖症脂肪组织炎症发病机制中的重要意义。先前报道的未经治疗的肥胖患者中CLS的丰度及其在减肥手术后的减少表明，CLS内的NLRP3-Caspase-1轴可能是减肥手术相关有益代谢作用的重要中介。

{"title":"NLRP3-Caspase-1 Axis in Human Adipose Tissue Crown-Like Structures: A Potential Mediator of Inflammation and the Effects of Bariatric Surgery","authors":"Ville A. Palomäki, Juha P. Väyrynen, Vesa Koivukangas, Sanna Meriläinen, Tuomo J. Karttunen, Petri Lehenkari","doi":"10.1002/iid3.70312","DOIUrl":"10.1002/iid3.70312","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Obesity-related comorbidities, such as type 2 diabetes, are associated with chronic inflammation mediated by macrophages. This inflammation is characterized by the accumulation of macrophages in crown-like structures (CLS) surrounding dead adipocytes within adipose tissue. In a recent study, we reported a significant reduction in CLS-associated macrophages following bariatric surgery. The NLRP3 inflammasome and its downstream effector, Caspase-1, are well-established mediators of metabolic dysfunction and inflammation in obesity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Immunohistochemical single- and multiplex staining of subcutaneous adipose tissue (SAT) samples from patients with obesity was performed to characterize the detailed distribution of NLRP3 and Caspase-1. The samples were collected during gastric bypass surgery and at a 1-year follow-up.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Both NLRP3 and Caspase-1 were expressed by CD68-positive macrophages in SAT including both single macrophages and those forming CLS. A reduction in the total number of SAT macrophages expressing these proteins was detected following gastric bypass. Furthermore, NLRP3 and Caspse-1 were observed in the endothelium of vascular structures.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our findings demonstrate that both CLS-forming and single cell macrophage populations in human adipose tissue express NLRP3 and Caspase-1. The study highlights the significance of the NLRP3 inflammasome macrophages in the pathogenesis of adipose tissue inflammation in obesity. The previously reported abundance of CLS in untreated obesity and their reduction after bariatric surgery suggest that the NLRP3-Caspase-1 axis within CLS may serve as an important mediator of the beneficial metabolic effects associated with bariatric surgery.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13289,"journal":{"name":"Immunity, Inflammation and Disease","volume":"14 2","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12877315/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146124780","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

Integrative Omics Analysis Reveals the Potential Value of CEACAM6 in Pan-Gastrointestinal Cancers 综合组学分析揭示CEACAM6在泛胃肠道癌症中的潜在价值。

IF 2.7 4区医学 Q3 IMMUNOLOGY

Immunity, Inflammation and Disease

Pub Date : 2026-02-04 DOI: 10.1002/iid3.70327

Liying Jin, Changjuan Tao, Zhiyong Pan, Peng Zhang

Objective

Carcinoembryonic antigen cell adhesion molecule 6 (CEACAM6) is known as a cell adhesion receptor which could regulate proliferation and other signaling in cancer. The role of CEACAM6 in pan-gastrointestinal cancers remains largely uncharacterized. This study employed multi-omics bioinformatics to investigate the expression distribution, prognostic value, and immune function of CEACAM6 in these malignancies.

Methods

Utilizing multi-omics data from The Cancer Genome Atlas (TCGA), cBioPortal, GDSC2, TIMER2.0, and TISCH databases, we assessed the CEACAM6 expression and prognostic value across pan-gastrointestinal cancers. Additionally, the potential role of CEACAM6 in the tumor immune microenvironment was explored using multi-omics data, including spatial transcriptomics data.

Results

Based on TCGA data, CEACAM6 was found to be overexpressed in pan-gastrointestinal cancers. The CEACAM6 somatic copy number alterations, DNA methylation and mutation sites were identified as potential contributors to abnormal CEACAM6 expression. The CEACAM6 expression was significantly negatively associated with the abundance of CD4 + Th1 cells across pan-gastrointestinal cancers. Furthermore, spatial transcriptomics data revealed that CEACAM6 expression was significant positively associated with malignant cells, while there was a negative correlation was observed with between CEACAM6 expression and plasma cells.

Conclusion

CEACAM6 exhibits high diagnostic accuracy and tumor-specific overexpression in pan-gastrointestinal cancers. CEACAM6 could promote angiogenesis/metastasis and suppress anti-tumor immunity. Spatially localized in tumors with immune cell exclusion, CEACAM6 correlates with poor survival and immune-excluded subtypes, positioning it as a therapeutic target in precision immunotherapy for pan-gastrointestinal cancers.

目的：癌胚抗原细胞粘附分子6 （CEACAM6）被认为是一种细胞粘附受体，可调节肿瘤细胞增殖及其他信号传导。CEACAM6在泛胃肠道癌症中的作用在很大程度上仍未明确。本研究采用多组学生物信息学方法研究CEACAM6在这些恶性肿瘤中的表达分布、预后价值和免疫功能。方法：利用来自癌症基因组图谱（TCGA）、cbiopportal、GDSC2、TIMER2.0和TISCH数据库的多组学数据，评估CEACAM6在泛胃肠道癌症中的表达及其预后价值。此外，我们还利用多组学数据（包括空间转录组学数据）探索了CEACAM6在肿瘤免疫微环境中的潜在作用。结果：基于TCGA数据，CEACAM6在泛胃肠癌中过表达。CEACAM6体细胞拷贝数改变、DNA甲基化和突变位点被确定为CEACAM6异常表达的潜在因素。CEACAM6的表达与泛胃肠道肿瘤中CD4 + Th1细胞的丰度呈显著负相关。此外，空间转录组学数据显示CEACAM6表达与恶性细胞呈显著正相关，而与浆细胞呈负相关。结论：CEACAM6在泛胃肠道肿瘤中具有较高的诊断准确性和肿瘤特异性过表达。CEACAM6具有促进血管生成/转移和抑制抗肿瘤免疫的作用。CEACAM6在免疫细胞排斥的肿瘤中存在空间定位，与生存差和免疫排斥亚型相关，将其定位为泛胃肠道癌症精确免疫治疗的治疗靶点。

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引用次数: 0

Bufalin Inhibits Cytokine Storm by Regulating TLR4/TLR3 Signaling Pathway 蟾毒灵通过调节TLR4/TLR3信号通路抑制细胞因子风暴

IF 2.7 4区医学 Q3 IMMUNOLOGY

Immunity, Inflammation and Disease

Pub Date : 2026-02-04 DOI: 10.1002/iid3.70318

Xixi Liu, Chencheng Li, Jing Yang, Weiguang Zhang, Zhongxiao Hu, Xiaoli Zhang, Reaila Jianati, Fang Tian, Xingbin Dai, Zuqiong Xu, Biqing Chen, Xuejun Zhu

Background

Bufalin is one main component of the dried venom from Bufo gargarizans Cantor, which has anti-tumor, cardiotonic, anti-inflammatory and other physiological activities. However, in recent years, researchers have mainly paid attention to its anti-tumor effect and neglected its anti-inflammatory effect.

Methods

We used lipopolysaccharide (TLR4 ligand) and poly inosinic acid (TLR3 ligand) to stimulate cultured macrophages to induce inflammatory condition. Transcriptome sequencing and molecular experiments were performed to investigate the underlying mechanism.

Results

Bufalin could significantly reduce the production of pro-inflammatory factors (IL-6, TNF-α, IL-1β, IL-8, CXCL10, etc.), through inhibiting the phosphorylation of IKBα and IRF3, and thus down-regulating Toll-like receptor pathway. Molecular docking predicted that one of the molecular targets of bufalin is MD-2 coupled with lipopolysaccharide-activated TLR4.

Conclusion

These findings not only support the pharmacological basis of using toad to treat inflammatory diseases in the Chinese medical history, but also provide a promising anti-inflammatory drug candidate for future clinical application.

背景：蟾毒灵是大蟾蜍干毒液的主要成分之一，具有抗肿瘤、强心、抗炎等生理活性。然而，近年来研究人员主要关注其抗肿瘤作用，而忽视了其抗炎作用。方法：采用脂多糖（TLR4配体）和多肌苷酸（TLR3配体）刺激培养巨噬细胞诱导炎症。通过转录组测序和分子实验研究其潜在机制。结果：蟾毒灵可通过抑制IKBα和IRF3的磷酸化，从而下调toll样受体通路，显著降低促炎因子（IL-6、TNF-α、IL-1β、IL-8、CXCL10等）的产生。分子对接预测蟾毒灵的分子靶点之一是MD-2偶联脂多糖活化的TLR4。结论：这些发现不仅支持了中国医学史上利用蟾蜍治疗炎症性疾病的药理学基础，也为今后临床应用提供了一种有前景的抗炎候选药物。

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引用次数: 0

DUSP1 Attenuates Renal Injury in Diabetic Nephropathy by Modulating Ferroptosis: Evidence From Animal Experiments DUSP1通过调节铁下垂减轻糖尿病肾病的肾损伤：来自动物实验的证据。

IF 2.7 4区医学 Q3 IMMUNOLOGY

Immunity, Inflammation and Disease

Pub Date : 2026-02-04 DOI: 10.1002/iid3.70340

Jiarong Liu, Junping Zhang, Yun Zou, Wen Chen, Jixiong Xu

<div> <section> <h3> Objective</h3> <p>Emerging evidence suggests that ferroptosis contributes significantly to the progression of diabetic nephropathy (DN). This study aimed to explore the potential association between dual specificity phosphatase 1 (DUSP1) and ferroptosis in a streptozotocin-induced DN rat model.</p> </section> <section> <h3> Methods</h3> <p>We analyzed microarray datasets (GSE30122 and GSE96804) from the gene expression omnibus (GEO) database to identify ferroptosis-related differentially expressed genes (FDEGs), with particular focus on DUSP1. Experimental validation was performed using 45 specific pathogen-free Sprague-Dawley rats: 15 controls and 30 STZ-induced DN models (60 mg/kg, i.p.). After 12 weeks, successfully modeled rats (<i>n</i> = 28) were randomized into DN (<i>n</i> = 14) and DN+Ferrostatin-1 (Fer-1, a ferroptosis inhibitor, 2.5 μmol/kg, <i>n</i> = 14) groups. Renal function parameters (blood urea nitrogen, serum creatinine, urinary albumin) were quantified using automated biochemical analysis. Renal tissue antioxidant capacity (SOD, GSH, MDA) and iron content were assessed. Histopathological evaluation employed HE, Masson, PAS, and Lillie staining. DUSP1 expression was analyzed via immunohistochemistry, Western blot, and RT-qPCR.</p> </section> <section> <h3> Results</h3> <p>DN rats exhibited characteristic metabolic disturbances including polydipsia (394.32 ± 9.92 vs. 28.84 ± 2.45 mL/day, <i>p</i> < 0.001), polyuria, and progressive weight loss. Renal function impairment was evidenced by elevated blood urea nitrogen (2.50 ± 0.46 vs. 11.61 ± 1.61 mmol/L, <i>p</i> < 0.001), serum creatinine (43.01 ± 5.81 vs. 107.62 ± 9.90 μmol/L, <i>p</i> < 0.001), and urine albumin-to-creatinine ratio (18.53 ± 0.92 vs. 269.97 ± 24.59 mg/g, <i>p</i> < 0.001). Fer-1 treatment significantly ameliorated these parameters (<i>p</i> < 0.05) and reduced histopathological damage. DN rats exhibited significantly reduced DUSP1 expression and increased ferroptosis-associated alterations, including elevated ACSL4 expression, enhanced lipid peroxidation, and impaired antioxidant capacity, all of which were partially reversed by Fer-1 treatment (<i>p</i> < 0.001).</p> </section> <section> <h3> Conclusions</h3> <p>Our findings indicate that inhibition of ferroptosis attenuates renal injury in DN and is accompanied by altered DUSP1 expression. These results suggest a potential association between ferroptosis regulation and DUSP1 in DN, providing new insight into ferroptosis-related mechanisms involved in disease progression.</p

目的：越来越多的证据表明，铁下垂在糖尿病肾病（DN）的进展中起着重要作用。本研究旨在探讨双特异性磷酸酶1 （DUSP1）与链脲佐菌素诱导的DN大鼠模型中铁下垂的潜在关联。方法：分析基因表达综合数据库（GEO）中的微阵列数据集（GSE30122和GSE96804），以DUSP1为重点，鉴定与铁衰相关的差异表达基因（FDEGs）。采用45只无特定病原体的Sprague-Dawley大鼠、15只对照组和30只stz诱导DN模型（60 mg/kg, i.p.）进行实验验证。12周后，成功造模的大鼠（n = 28）随机分为DN组（n = 14）和DN+铁抑素-1组（铁抑素-1,2.5 μmol/kg, n = 14）。采用全自动生化分析定量测定肾功能参数（血尿素氮、血清肌酐、尿白蛋白）。测定肾组织抗氧化能力（SOD、GSH、MDA）和铁含量。组织病理学评价采用HE、Masson、PAS和Lillie染色。通过免疫组织化学、Western blot和RT-qPCR分析DUSP1的表达。结果：DN大鼠表现出特征性的代谢紊乱，包括多饮（394.32±9.92 vs 28.84±2.45 mL/d） p。结论：我们的研究结果表明，抑制铁下垂可减轻DN的肾损伤，并伴有DUSP1表达的改变。这些结果表明，在DN中，铁下垂调节与DUSP1之间存在潜在的关联，为参与疾病进展的铁下垂相关机制提供了新的见解。

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引用次数: 0

Navigating the Complexities of Pemphigus Vulgaris: A Comprehensive Iranian Study 导航寻常性天疱疮的复杂性：一项全面的伊朗研究。

IF 2.7 4区医学 Q3 IMMUNOLOGY

Immunity, Inflammation and Disease

Pub Date : 2026-02-04 DOI: 10.1002/iid3.70317

Delaram Moosavi, Seyed Mohammad Mahdi Khadem, Afsaneh Sadeghzadeh Bazargan, Kambiz Kamyab Hesari, Mehrnaz Azh, Hamed Zarei Sharif, Nasrin Shayanfar, Azadeh Goodarzi

Introduction

Pemphigus vulgaris (PV) is a rare, severe autoimmune disorder characterized by the production of autoantibodies that cause blistering of the skin and mucous membranes, often presenting with oral lesions in 50%–70% of cases. It has a global incidence of 0.5–3.2 per 100,000 people, with variations across regions, and in Iran, the rate is about 1 per 100,000 annually. PV affects both sexes equally and typically manifests in the sixth decade of life, though the age of onset varies internationally, tending to be younger in India and Western countries.

Methodology

In this cross-sectional study, data were collected from 63 patients diagnosed with PV via telephone interviews. This project was approved by the Research Ethics Committee of Iran University of Medical Sciences. Statistical analyses were performed using SPSS software, version 22.0 (IBM Corp., Armonk, NY, USA).

Results

Among 63 PV patients, 56% were female, and 44% were male, with an average age of 50.17 years and a mean age of onset of 44.91 years (SD = 14.77). Most patients (70%) initially presented with mucosal symptoms, and the average time to diagnosis was approximately 17 months. Common misdiagnoses included aphthous ulcers, lichen planus, and allergic reactions. After diagnosis, most patients (82%) received multiple medications. The most frequently used medications were prednisolone (50 patients, 84.75%), methylprednisolone (10 patients, 16.9%), and rituximab (34 patients, 57.63%).

Discussion

PV in this cohort most often began with mucosal symptoms and was frequently preceded by consultations with non-dermatology clinicians, contributing to diagnostic delays. Such delays may negatively affect.

寻常型天疱疮（Pemphigus vulgaris， PV）是一种罕见的、严重的自身免疫性疾病，其特征是产生自身抗体，导致皮肤和粘膜起泡，通常在50%-70%的病例中表现为口腔病变。全球发病率为每10万人中有0.5-3.2例，各地区有所不同，在伊朗，发病率约为每年每10万人中有1例。PV对两性的影响是平等的，通常在生命的第六个十年出现，尽管发病年龄在国际上有所不同，在印度和西方国家往往更年轻。方法：在这项横断面研究中，通过电话访谈收集了63名确诊为PV的患者的数据。本项目获得伊朗医科大学研究伦理委员会批准。统计学分析采用SPSS软件，version 22.0 （IBM Corp., Armonk， NY， USA）。结果：63例PV患者中女性占56%，男性占44%，平均年龄50.17岁，平均发病年龄44.91岁（SD = 14.77）。大多数患者（70%）最初表现为粘膜症状，平均诊断时间约为17个月。常见的误诊包括口腔溃疡、扁平苔藓和过敏反应。确诊后，大多数患者（82%）接受了多种药物治疗。最常用的药物是强的松龙（50例，84.75%）、甲基强的松龙（10例，16.9%）和美罗华（34例，57.63%）。讨论：该队列中的PV最常以粘膜症状开始，并且在此之前经常咨询非皮肤科临床医生，导致诊断延迟。这种延误可能会产生负面影响。

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引用次数: 0

Advances in the Role of Adipose Tissue in Promoting Injury Repair and Resist Infection 脂肪组织促进损伤修复和抗感染作用的研究进展。

IF 2.7 4区医学 Q3 IMMUNOLOGY

Immunity, Inflammation and Disease

Pub Date : 2026-02-04 DOI: 10.1002/iid3.70341

Xi Duan, Run Li, Lei Fu, Jiali Yang, Zhean Zhan

Background

In recent years, adipose tissue (AT) transplantation has increasingly been noticed by many people in the field of tissue repair and regeneration. Accumulating evidence demonstrates that AT exerts dual functions in promoting tissue repair and conferring anti-infective properties, with distinct biological effects attributed to its heterogeneous components.

Objective

This review systematically examines the distribution of AT and its components, including adipocytes, extracellular matrix (ECM), immune cells, stromal vascular fraction (SVF), and adipokines. Distinct AT components mediate tissue repair and infection resistance through unique molecular mechanisms.

Results

Functionally, adipocytes and immune cells secrete various cytokines, including adiponectin, leptin, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), antimicrobial peptides, and IL-17, which coordinate inflammatory signaling and enhance host defense mechanisms. The main function of the ECM is to provide structural support for cells. SVF cell populations exhibit dual functionality: accelerating neural and cutaneous regeneration while suppressing fibrotic pathways to minimize scar formation.

Conclusion

Recommendations are proposed to guide future investigations into AT-mediated immune functions. This review highlights potential strategies for advancing AT-based clinical therapeutics and suggests novel directions for foundational studies on AT's anti-infective mechanisms.

背景：近年来，脂肪组织（AT）移植在组织修复和再生领域越来越受到人们的关注。越来越多的证据表明，AT在促进组织修复和赋予抗感染特性方面具有双重功能，由于其成分的异质性，具有不同的生物学效应。目的：本综述系统地研究了脂肪细胞、细胞外基质（ECM）、免疫细胞、基质血管组分（SVF）和脂肪因子等AT及其组分的分布。不同的AT成分通过独特的分子机制介导组织修复和感染抵抗。结果：在功能上，脂肪细胞和免疫细胞分泌多种细胞因子，包括脂联素、瘦素、肿瘤坏死因子-α (TNF-α)、白细胞介素-6 （IL-6）、抗菌肽和IL-17，协调炎症信号，增强宿主防御机制。ECM的主要功能是为细胞提供结构支持。SVF细胞群表现出双重功能：加速神经和皮肤再生，同时抑制纤维化途径以减少疤痕形成。结论：为进一步研究at介导的免疫功能提出了建议。这篇综述强调了推进AT临床治疗的潜在策略，并为AT抗感染机制的基础研究提出了新的方向。

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引用次数: 0

Investigating the Role of A20 in Respiratory Syncytial Virus Immunopathogenesis in a BALB/c Mouse Model 在BALB/c小鼠模型中研究A20在呼吸道合胞病毒免疫发病机制中的作用。

IF 2.7 4区医学 Q3 IMMUNOLOGY

Immunity, Inflammation and Disease

Pub Date : 2026-02-04 DOI: 10.1002/iid3.70337

Alireza Tahamtan, Mohammad Yasaghi, Saeed Samadizadeh, Hadi Razavi Nikoo, Ahad Yamchi, Vahid Salimi

Background

Respiratory syncytial virus (RSV) is a leading cause of acute respiratory tract infections in children and the elderly worldwide. RSV pathogenesis is largely driven by exaggerated host immune responses that result in lung injury. In this study, we examined the role of A20 (TNFAIP3), a key regulator of immune signaling, in RSV infection using a BALB/c mouse model.

Methods

Recombinant lentiviruses encoding TNFAIP3 (A20) or A20-specific shRNA were generated and administered to BALB/c mice. Animals received intravenous lentivectors, challenged intranasally with RSV-A2, and sacrificed on Day 5 postinfection. A20 expression, cytokine and chemokine levels, lung pathology, and viral load were assessed using real-time polymerase chain reaction (RT-PCR), enzyme-linked immunosorbent assay (ELISA), and histopathological analysis.

Results

RSV infection significantly induced A20 expression in bronchoalveolar (BAL) cells. Lentivector-mediated modulation of A20 expression produced distinct outcomes: A20 downregulation amplified inflammatory responses, increased immune cell infiltration, and elevated pro-inflammatory mediator secretion in BAL fluid, leading to aggravated lung pathology. In contrast, A20 upregulation did not markedly alter immune cell recruitment, cytokine production, or histopathological changes following RSV infection.

Conclusion

A20 downregulation exacerbates inflammation and lung injury following RSV infection, highlighting its critical role in immune regulation during the virus infection. Further studies employing targeted molecular delivery systems and human airway organoid models are warranted to evaluate the therapeutic potential of modulating A20 in RSV disease.

背景：呼吸道合胞病毒（RSV）是全世界儿童和老年人急性呼吸道感染的主要原因。RSV的发病机制主要是由过度的宿主免疫反应引起的，从而导致肺损伤。在这项研究中，我们使用BALB/c小鼠模型检测了A20 （TNFAIP3）在RSV感染中的作用，这是免疫信号的关键调节因子。方法：制备编码TNFAIP3 （A20）或A20特异性shRNA的重组慢病毒，并给予BALB/c小鼠。动物接受慢体载体静脉注射，鼻内感染RSV-A2，感染后第5天处死。采用实时聚合酶链反应（RT-PCR）、酶联免疫吸附试验（ELISA）和组织病理学分析评估A20表达、细胞因子和趋化因子水平、肺部病理和病毒载量。结果：RSV感染显著诱导支气管肺泡（BAL）细胞A20表达。慢载体介导的A20表达调节产生了不同的结果：A20下调放大炎症反应，增加免疫细胞浸润，BAL液中促炎介质分泌升高，导致肺部病理加重。相比之下，A20上调并没有显著改变RSV感染后的免疫细胞募集、细胞因子产生或组织病理学变化。结论：A20下调可加重RSV感染后的炎症和肺损伤，凸显其在病毒感染过程中免疫调节的重要作用。有必要进一步研究靶向分子传递系统和人类气道类器官模型，以评估调节A20在RSV疾病中的治疗潜力。

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引用次数: 0