Immunobiology最新文献_第10页

Expression of miR-146a in Th17 cells from rheumatoid arthritis patients and its correlation with inflammatory cytokines 类风湿关节炎患者Th17细胞中miR-146a的表达及其与炎症因子的相关性

IF 2.5 4区医学 Q3 IMMUNOLOGY

Immunobiology

Pub Date : 2025-05-01 Epub Date: 2025-05-22 DOI: 10.1016/j.imbio.2025.152916

Jinhui Tan , Linghua Tan , Hai Huang , Bo Li

To investigate the expression of miR-146a in peripheral blood T helper 17(Th17) cells of patients with rheumatoid arthritis (RA) and its correlation with inflammatory cytokines [tumor necrosis factor-α (TNF-α), interleukin-6(IL-6) and interleukin-17(IL-17)]. 50 patients with active RA who were treated in People's Hospital of Longhua, Shenzhen from July 2022 to June 2024 were selected, and 50 healthy people who underwent physical examination in the hospital during the same period were selected as healthy controls. Peripheral blood mononuclear cells(PBMCs) and Th cells were isolated from the venous blood of the subjects in the two groups. Quantitative real-time PCR (qPCR) was used to detect the expression of miR-146a in peripheral blood Th17 cells of the two groups, and flow cytometry (FCM) was used to detect the levels of TNF-α, IL-6 and IL-17. The peripheral blood Th17 cells of RA patients were transfected with miR-146a mimic, and the expression of miR-146a, TNF-α, IL-6 and IL-17 was detected again after transfection. Pearson correlation coefficient was used to analyze the correlation between miR-146a expression and TNF-α, IL-6, and IL-17 expression in RA patients before and after transfection. Before transfection of miR-146a mimic, the expression of miR-146a, TNF-α, IL-6, and IL-17 in peripheral blood Th17 cells of RA patients was higher than that of healthy controls(P = 0.000). After transfection, the expression level of miR-146a in peripheral blood Th17 cells of RA patients increased compared to before transfection, while the expressions of TNF-α, IL-6, and IL-17 decreased(P = 0.000). Pearson correlation analysis showed that the expression level of miR-146a in peripheral blood Th17 cells of RA patients before transfection was positively correlated with the expression levels of TNF-α, IL-6, and IL-17(r = 0.968, P = 0.000; r = 0.980, P = 0.000; r = 0.993, P = 0.000). After transfection, the expression level of miR-146a was also positively correlated with the expression levels of TNF-α, IL-6, and IL-17(r = 0.971, P = 0.000; r = 0.963, P = 0.000; r = 0.970, P = 0.000). miR-146a may participate in the pathogenesis of RA to some extent by affecting the secretion of TNF-α, IL-6, IL-17, and other related inflammatory cytokines by Th17 cells in peripheral blood of RA patients.

探讨miR-146a在类风湿关节炎（RA）患者外周血T辅助17（Th17）细胞中的表达及其与炎症因子[肿瘤坏死因子-α (TNF-α)、白细胞介素-6（IL-6）、白细胞介素-17(IL-17)]的相关性。选择2022年7月至2024年6月在深圳市龙华人民医院治疗的50例活动期RA患者，选择同期在该院体检的健康人群50例作为健康对照。从两组受试者静脉血中分离外周血单个核细胞（PBMCs）和Th细胞。采用实时荧光定量PCR （qPCR）检测两组患者外周血Th17细胞中miR-146a的表达，采用流式细胞术（FCM）检测TNF-α、IL-6、IL-17的水平。将miR-146a mimic转染RA患者外周血Th17细胞，转染后再次检测miR-146a、TNF-α、IL-6、IL-17的表达。采用Pearson相关系数分析转染前后RA患者miR-146a表达与TNF-α、IL-6、IL-17表达的相关性。转染miR-146a mimic前，RA患者外周血Th17细胞中miR-146a、TNF-α、IL-6、IL-17的表达均高于健康对照组（P = 0.000）。转染后，RA患者外周血Th17细胞中miR-146a表达水平较转染前升高，TNF-α、IL-6、IL-17表达水平下降（P = 0.000）。Pearson相关分析显示，转染前RA患者外周血Th17细胞中miR-146a的表达水平与TNF-α、IL-6、IL-17的表达水平呈正相关(r = 0.968, P = 0.000；r = 0.980, P = 0.000；r = 0.993, P = 0.000)。转染后miR-146a的表达水平也与TNF-α、IL-6、IL-17的表达水平呈正相关(r = 0.971, P = 0.000；r = 0.963, P = 0.000；r = 0.970, P = 0.000)。miR-146a可能通过影响RA患者外周血Th17细胞分泌TNF-α、IL-6、IL-17等相关炎性细胞因子，在一定程度上参与RA的发病过程。

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引用次数: 0

CH25H/25-HC promotes pulmonary fibrosis via AMPK/STAT6 pathway-dependent M2 macrophage polarization in COPD CH25H/25-HC通过AMPK/STAT6通路依赖的M2巨噬细胞极化促进COPD肺纤维化

IF 2.5 4区医学 Q3 IMMUNOLOGY

Immunobiology

Pub Date : 2025-05-01 Epub Date: 2025-04-24 DOI: 10.1016/j.imbio.2025.152908

Ying Li, Guangzhi Xiao, Xianghui Fu, Xing Luo, Fengfan Yang, Yadan Li, Zhaohui Zheng

Objective

Chronic obstructive pulmonary disease (COPD) is intricately linked to pulmonary fibrosis, yet the underlying mechanisms remain unclear. This study investigates whether CH25H/25-hydroxycholesterol (25-HC) promotes pulmonary fibrosis in COPD by modulating AMPK/STAT6-dependent M2 macrophage polarization.

Methods

Using GEO datasets and a cigarette smoke-induced COPD mouse model, we analyzed CH25H expression and fibrotic pathology. CH25H was silenced via adeno-associated virus (AAV)-delivered shRNA. Histopathology, flow cytometry, qPCR, and Western blotting assessed fibrosis, macrophage polarization (M1/M2), and AMPK/STAT6 pathway activity. Bone marrow-derived macrophages (BMDMs) were employed to validate polarization mechanisms. The role of the AMPK/STAT6 pathway was investigated using the specific activator.

Results

Analysis of the GEO database and experimental verification showed significantly increased CH25H expression in both lung tissues and macrophages from COPD mice. CH25H knockdown alleviated alveolar damage, airway remodeling, and pulmonary fibrosis in COPD mice, evidenced by reduced expression of fibrosis-related proteins, improved lung function, and attenuated inflammatory responses. Moreover, CH25H knockdown inhibited M2 macrophage polarization and decreased the proportion of M2-type macrophages. Importantly, decreased levels of 25-HC following CH25H knockdown were asso ciated with suppressed activation of the AMPK/STAT6 pathway. Rescue experiments demonstrated that the protective effects of CH25H knockdown could be reversed by adding the AMPKα activator GSK621.

Conclusion

Our findings demonstrate that CH25H/25-HC exacerbates COPD-associated pulmonary fibrosis by promoting AMPK/STAT6-dependent M2 macrophage polarization. Targeting CH25H may represent a novel therapeutic strategy for mitigating fibrosis in COPD.

慢性阻塞性肺疾病（COPD）与肺纤维化有着复杂的联系，但其潜在机制尚不清楚。本研究探讨CH25H/25-羟基胆固醇（25-HC）是否通过调节AMPK/ stat6依赖性M2巨噬细胞极化促进COPD肺纤维化。方法使用GEO数据集和香烟烟雾诱导的COPD小鼠模型，分析CH25H的表达和纤维化病理。通过腺相关病毒（AAV）递送shRNA使CH25H沉默。组织病理学、流式细胞术、qPCR和Western blotting评估纤维化、巨噬细胞极化（M1/M2）和AMPK/STAT6通路活性。骨髓源性巨噬细胞（bmdm）被用来验证极化机制。使用特异性激活剂研究AMPK/STAT6通路的作用。结果GEO数据库分析和实验验证显示，慢性阻塞性肺病小鼠肺组织和巨噬细胞中CH25H表达均显著升高。CH25H敲低可减轻COPD小鼠的肺泡损伤、气道重塑和肺纤维化，这可以通过纤维化相关蛋白的表达降低、肺功能改善和炎症反应减弱来证明。CH25H敲低抑制M2型巨噬细胞极化，降低M2型巨噬细胞比例。重要的是，CH25H敲除后25-HC水平的降低与AMPK/STAT6通路的抑制激活有关。救援实验表明，添加AMPKα激活剂GSK621可以逆转CH25H敲低的保护作用。结论CH25H/25-HC通过促进AMPK/ stat6依赖性M2巨噬细胞极化，加重copd相关肺纤维化。靶向CH25H可能是缓解COPD纤维化的一种新的治疗策略。

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引用次数: 0

Different doses of hydroxychloroquine regulate the structure of intestinal flora and glycosyltransferase activity in rats with IgA nephropathy 不同剂量羟氯喹对IgA肾病大鼠肠道菌群结构及糖基转移酶活性的影响

IF 2.5 4区医学 Q3 IMMUNOLOGY

Immunobiology

Pub Date : 2025-05-01 Epub Date: 2025-03-12 DOI: 10.1016/j.imbio.2025.152891

Lingling Bao, Xueyan Bian, Liling Ren, Sizeng Bao, Aiwei Zhang

Background

Hydroxychloroquine (HCQ), by virtue of its ability to reduce proteinuria, is an alternative therapy for Immunoglobulin A nephropathy (IgAN). This study investigated the effects of different doses of HCQ on the structure of intestinal flora and glycosyltransferase activity in IgAN rats.

Methods

IgAN model rats constructed by treatment of bovine serum albumin, castor oil and lipopolysaccharide were administered with HCQ (18 or 36 mg/kg) by gavage. Then the number of urine erythrocyte and the renal function of rats were evaluated. The levels of galactose-deficient IgA1 (Gd-IgA1), B cell activation factor (BAFF) and C-reactive protein (CRP) in serum and those of inflammatory factors in renal tissue were detected by ELISA. Renal tissue injury and IgA deposition were assessed by histological analysis. The expressions of Core 1 beta1,3-galactosyltransferase (C1GALT1), Core 1 synthase specific molecular chaperone (COSMC) and ST6 N-acetylgalactosaminide alpha-2,6-sialyltransferase 2 (ST6GALNAC2) were quantified by qRT-PCR, Western blot or in vitro enzyme assays. 16 s rDNA sequencing was used to analyze the structure of intestinal flora in rats.

Results

HCQ dose-dependently decreased the levels of serum creatinine, UREA, Gd-IgA1, BAFF, CRP and urine protein, waned the number of urine erythrocyte, inhibited the expressions of inflammatory factors and IgA deposition in renal tissue, and up-regulated the expressions of C1GALT1, COSMC and down-regulated ST6GALNAC2 expression in peripheral blood mononuclear cells (PBMCs).

Conclusion

HCQ could reduce glomerular swelling in mesangial area and improve the imbalance of intestinal flora in IgAN rats.

背景：羟氯喹（HCQ）由于其减少蛋白尿的能力，是免疫球蛋白A肾病（IgAN）的一种替代疗法。本研究探讨了不同剂量的HCQ对IgAN大鼠肠道菌群结构和糖基转移酶活性的影响。方法以牛血清白蛋白、蓖麻油、脂多糖处理的sigan模型大鼠分别灌胃HCQ（18、36 mg/kg）。然后观察大鼠尿红细胞数和肾功能的变化。采用ELISA法检测血清中半乳糖缺乏IgA1 （Gd-IgA1）、B细胞活化因子（BAFF）、c反应蛋白（CRP）水平及肾组织炎症因子水平。采用组织学方法观察肾组织损伤及IgA沉积情况。采用qRT-PCR、Western blot或体外酶法检测core1 β - 1,3-半乳糖转移酶（C1GALT1）、core1合成酶特异性分子伴侣（COSMC）和ST6 n -乙酰半乳糖胺α -2,6-唾液转移酶2 （ST6GALNAC2）的表达。采用16s rDNA测序法分析大鼠肠道菌群结构。结果shcq呈剂量依赖性降低血清肌酐、尿素、Gd-IgA1、BAFF、CRP和尿蛋白水平，减少尿红细胞数量，抑制肾组织炎症因子表达和IgA沉积，上调外周血单核细胞C1GALT1、COSMC表达，下调ST6GALNAC2表达。结论hcq能减轻IgAN大鼠肾小球系膜区肿胀，改善肠道菌群失衡。

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引用次数: 0

Targeting B7-H3 in solid tumors: Development and evaluation of novel CAR-T Cell therapy 靶向B7-H3的实体肿瘤：新型CAR-T细胞疗法的发展和评估

IF 2.5 4区医学 Q3 IMMUNOLOGY

Immunobiology

Pub Date : 2025-05-01 Epub Date: 2025-03-14 DOI: 10.1016/j.imbio.2025.152888

Ning Li , Chunhua Zhang , Xiaoyu Li , Shufen Liu , Youhua Xu , Xifei Yang

Ovarian and gastric cancers, representative of many solid tumors, remain among the most challenging malignancies to treat due to limited therapeutic options and poor outcomes at advanced stages. Although immunotherapies have revolutionized cancer treatment, their efficacy in solid tumors has been hindered by issues such as antigen heterogeneity and the immunosuppressive tumor microenvironment. This study presents the development and evaluation of third-generation chimeric antigen receptor T (CAR-T) cells targeting B7-H3, an immune checkpoint molecule widely overexpressed in solid tumors. The B7-H3 CAR-T cells exhibited robust and selective cytotoxicity against B7-H3-positive tumor cells, sparing normal tissues. In preclinical animal models, these cells significantly inhibited tumor growth, demonstrating higher targeting specificity and preferential accumulation in tumor sites. These results highlight B7-H3-targeted CAR-T cells as a potential breakthrough in immunotherapy for solid tumors, offering a foundation for future clinical trials to refine their safety and efficacy.

卵巢癌和胃癌作为许多实体肿瘤的代表，由于治疗选择有限和晚期预后不佳，仍然是最具挑战性的恶性肿瘤之一。尽管免疫疗法已经彻底改变了癌症治疗，但它们在实体肿瘤中的疗效一直受到抗原异质性和免疫抑制肿瘤微环境等问题的阻碍。本研究提出了靶向B7-H3的第三代嵌合抗原受体T （CAR-T）细胞的开发和评估，B7-H3是一种在实体瘤中广泛过表达的免疫检查点分子。B7-H3 CAR-T细胞对B7-H3阳性肿瘤细胞表现出强大的选择性细胞毒性，不影响正常组织。在临床前动物模型中，这些细胞显著抑制肿瘤生长，表现出更高的靶向特异性和在肿瘤部位的优先积累。这些结果突出了b7 - h3靶向CAR-T细胞作为实体肿瘤免疫治疗的潜在突破，为未来的临床试验提供了基础，以完善其安全性和有效性。

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引用次数: 0

Assessment of cellular immune phenotype of peripheral blood mononuclear cells in Bangladeshi children with severe acute malnutrition 孟加拉国严重急性营养不良儿童外周血单个核细胞细胞免疫表型的评估

IF 2.5 4区医学 Q3 IMMUNOLOGY

Immunobiology

Pub Date : 2025-05-01 Epub Date: 2025-03-06 DOI: 10.1016/j.imbio.2025.152887

Zannatun Noor , Shaumik Islam , Md. Mehedi Hasan , Ar-Rafi Khan , Md Amran Gazi , Farzana Hossaini , Rashidul Haque , Tahmeed Ahmed , Mustafa Mahfuz

Children suffering from severe acute malnutrition (SAM) have a weakened immune system. The relationship between malnutrition and alterations in the frequency of peripheral blood mononuclear cells (PBMCs) remains unclear. This study investigated the altered immune responses in Bangladeshi children with SAM compared to healthy children. PBMCs were collected from 24 healthy children and 25 children with SAM upon their hospital admission and after 21 days of nutritional therapy at a nutritional rehabilitation unit. Flow cytometry was employed to assess various subsets of T cells, B cells, and natural killer (NK) cells. Children with SAM exhibited significantly lower levels of activated (CD25+) B cells (SAM vs. healthy: 0.18 % vs. 0.30 %, p = 0.031) and NK cells (SAM vs. healthy: 4.9 % vs. 9.6 %, p = 0.003) compared to healthy controls. Similar immune responses were observed in SAM children during both hospitalization and discharge, with NK cell percentages showing slight increases but remaining significantly lower than in healthy children (SAM endline vs. healthy: 5.9 % vs. 9.6 %, p = 0.032). Notable reductions were also observed in CD62+ helper T cells, CD62L+ cytotoxic T cells, and CD62L+ B cells. These results suggest that although SAM children recover clinically, their immune systems remain compromised during discharge.

患有严重急性营养不良（SAM）的儿童免疫系统较弱。营养不良与外周血单个核细胞（PBMCs）频率变化之间的关系尚不清楚。本研究调查了孟加拉国SAM儿童与健康儿童相比免疫反应的改变。从24名健康儿童和25名SAM儿童入院时和在营养康复单位接受21天营养治疗后收集pbmc。流式细胞术用于评估T细胞、B细胞和自然杀伤（NK）细胞的各种亚群。与健康对照相比，SAM患儿的活化（CD25+） B细胞（SAM vs.健康：0.18% vs. 0.30%, p = 0.031）和NK细胞（SAM vs.健康：4.9% vs. 9.6%, p = 0.003）水平显著降低。在住院和出院期间，SAM儿童观察到类似的免疫反应，NK细胞百分比略有增加，但仍显着低于健康儿童（SAM终末：5.9%对9.6%,p = 0.032）。在CD62+辅助性T细胞、CD62L+细胞毒性T细胞和CD62L+ B细胞中也观察到明显的减少。这些结果表明，尽管SAM儿童在临床上康复，但他们的免疫系统在出院时仍然受损。

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引用次数: 0

Single-cell RNA and TCR repertoire analysis identify markers of virus-specific T cells 单细胞RNA和TCR库分析鉴定病毒特异性T细胞的标记物

IF 2.5 4区医学 Q3 IMMUNOLOGY

Immunobiology

Pub Date : 2025-05-01 Epub Date: 2025-04-23 DOI: 10.1016/j.imbio.2025.152904

Byung-Kwan Jeong , Young-Ae Kim , Jung-Wook Park , Baknoon Ham , Jihyeong Kim , Gyungyub Gong , Chae Lyul Lim , Hee Jin Lee

Adoptive cell therapy (ACT) is a promising method for treating cancer and viral infections. Identifying antigen-specific T cells (ASTs) is critical to ACT. We investigated biomarkers for identifying ASTs. Peripheral blood mononuclear cells from healthy donors underwent staining with carboxyfluorescein succinimidyl ester (CFSE) to detect proliferating ASTs. Following exposure to CMV pp65 peptide and interleukin-2 for T-cell expansion, CD3⁺/CD8⁺ T cells were isolated at varying time points, revealing distinct populations. TCR repertoire analysis unveiled nine major clones in CFSE⁻/CD3⁺/CD8⁺ T cells on day 7, constituting 93.9 % of total cells. Contrarily, CFSE⁺/CD3⁺/CD8⁺ T cells exhibited minimal overlap with major TCR clones. Combined single-cell RNA-seq analyses highlighted upregulated genes associated with cell cycle proliferation and T-cell cytotoxicity. Engineered T cells expressing dominant clones effectively engaged CMV pp65 peptide, triggering T-cell activation and interferon-γ production. A set of seven upregulated genes in CFSE⁻/CD3⁺/CD8⁺ T cells on day 7, indicative of proliferating ASTs, was used to identify antigen-specific CD3⁺/CD8⁺ T cells on days 2–3, exhibiting 93.52 % accuracy. These markers predicted CFSE⁻/CD3⁺/CD8⁺ T cells with dominant TCR clones following exposure to EBV peptide with 74.59 % accuracy. In conclusion, we identified new markers facilitating the early isolation of viral antigen-responsive T cells.

过继细胞疗法（ACT）是一种很有前途的治疗癌症和病毒感染的方法。识别抗原特异性T细胞（ast）对ACT至关重要。我们研究了用于识别ast的生物标志物。健康供者外周血单个核细胞用羧基荧光琥珀酰亚胺酯（CFSE）染色检测增殖的ast。暴露于CMV pp65肽和白细胞介素-2进行T细胞扩增后，CD3+/CD8+ T细胞在不同时间点分离，显示不同的群体。TCR库分析在第7天发现CFSE−/CD3+/CD8+ T细胞中有9个主要克隆，占总细胞数的93.9%。相反，CFSE+/CD3+/CD8+ T细胞与主要TCR克隆的重叠最小。联合单细胞RNA-seq分析强调了与细胞周期增殖和t细胞毒性相关的上调基因。表达优势克隆的工程化T细胞有效地参与CMV pp65肽，触发T细胞活化和干扰素γ的产生。在第7天，CFSE−/CD3+/CD8+ T细胞中有7个表达上调的基因，指示ast增殖，用于鉴定第2-3天的抗原特异性CD3+/CD8+ T细胞，准确率为93.52%。这些标记物预测EBV肽暴露后具有显性TCR克隆的CFSE−/CD3+/CD8+ T细胞的准确率为74.59%。总之，我们发现了新的标记物，有助于早期分离病毒抗原反应性T细胞。

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引用次数: 0

Interpretable Machine Learning reveals the Role of PANoptosis in the Diagnosis and Subtyping of NAFLD 可解释的机器学习揭示了PANoptosis在NAFLD诊断和分型中的作用

IF 2.5 4区医学 Q3 IMMUNOLOGY

Immunobiology

Pub Date : 2025-05-01 Epub Date: 2025-04-26 DOI: 10.1016/j.imbio.2025.152909

Feng Tian , Yuqi Zhao , Xinyang He , Yu Zhang , Minxuan Hu , Yiwei Liang , Ziyou Tian , Yaxian Gao , Yongwei Wang

Non-alcoholic fatty liver disease (NAFLD) is a global health challenge characterized by complex pathogenesis and limited therapeutic options. Emerging evidence highlights PANoptosis—a coordinated interplay of pyroptosis, apoptosis, and necroptosis—as a critical driver of metabolic and immune dysregulation in NAFLD. Here, we integrated multiple datasets and interpretable machine learning to unravel the role of PANoptosis in NAFLD diagnosis, subtyping, and immune microenvironment remodeling. By intersecting differentially expressed genes and PANoptosis-related genes, we identified 9 hub genes (e.g., TRADD, CASP6, TNFRSF1A and TNFAIP3) and constructed a robust diagnostic model (AUC = 0.976) validated via SHAP analysis and nomogram. Unsupervised consensus clustering stratified NAFLD patients into two PANoptosis-driven subtypes (C1/C2 and CA/CB), revealing distinct immune cell infiltration patterns and pathway activation. Single-cell sequencing further localized hub genes to immune cells and revealed their cell communication, implicating their roles in the progression of NAFLD. Molecular docking studies identified fostamatinib and minocycline as potential therapeutic candidates, while pan-cancer analysis revealed that TNFRSF1A overexpression is associated with poor prognosis across multiple cancer types. This study enhances the understanding of PANoptosis as a crucial diagnostic and therapeutic target in NAFLD, providing novel insights into immune-mediated pathogenesis and paving the way for treatment strategies.

非酒精性脂肪性肝病（NAFLD）是一种全球性的健康挑战，其特点是发病机制复杂，治疗选择有限。新出现的证据表明，panoptosis（焦亡、凋亡和坏死的协调相互作用）是NAFLD代谢和免疫失调的关键驱动因素。在这里，我们整合了多个数据集和可解释的机器学习来揭示PANoptosis在NAFLD诊断、亚型分型和免疫微环境重塑中的作用。通过将差异表达基因与panoptoiss相关基因相交，鉴定出TRADD、CASP6、TNFRSF1A、TNFAIP3等9个枢纽基因，并通过SHAP分析和nomogram验证，构建了稳健的诊断模型（AUC = 0.976）。无监督共识聚类将NAFLD患者分为两种panoposis驱动亚型（C1/C2和CA/CB），揭示了不同的免疫细胞浸润模式和途径激活。单细胞测序进一步将枢纽基因定位到免疫细胞并揭示其细胞通讯，暗示其在NAFLD进展中的作用。分子对接研究确定福司他替尼和米诺环素是潜在的治疗候选者，而泛癌症分析显示TNFRSF1A过表达与多种癌症类型的不良预后相关。本研究增强了对PANoptosis作为NAFLD重要诊断和治疗靶点的认识，为免疫介导的发病机制提供了新的见解，并为治疗策略铺平了道路。

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引用次数: 0

Ureaplasma urealyticum GrpE protein elicits glycolysis-mediated inflammatory responses through TLR2 in macrophages 解脲原体GrpE蛋白通过TLR2在巨噬细胞中引发糖酵解介导的炎症反应

IF 2.5 4区医学 Q3 IMMUNOLOGY

Immunobiology

Pub Date : 2025-05-01 Epub Date: 2025-04-21 DOI: 10.1016/j.imbio.2025.152902

Jing Xie , Nan Xie , Chang Liu , Zhemin Huang , Min Du , Hao Hu , Kang Zheng , Jiaofeng Peng , Ranhui Li

The pathogenesis of Ureaplasma urealyticum infection is linked to the host inflammatory response; however, the specific molecular mechanisms underlying this phenomenon have not been fully elucidated. GrpE is a chaperonin that accelerates ADP release and ATP binding to DnaK, thereby enhancing the chaperone function of the HSP70 system under stress. However, alternative activities such as pro-inflammatory responses remain poorly understood. In this study, we report that the U. urealyticum GrpE exerts as a cytokine-inducing virulence factor toward macrophages. Using gene-knockout mice and specific inhibitors, we found that GrpE-induced pro-inflammatory cytokine expression was mediated by the TLR2/STAT3 pathway. We also found that glycolysis was essential for this pro-inflammatory response. Mechanistically, GrpE treatment stimulated STAT3-dependent accumulation of citric acid and acetyl-CoA, promoting histone acetylation and potent pro-inflammatory responses. Our results indicate that glycolysis plays a role in the inflammatory response induced by GrpE through the TLR2/STAT3 pathway and contributes to the glycolysis-mediated inflammatory response, offering a fresh understanding of the development of U. urealyticum infection.

尿解支原体感染的发病机制与宿主的炎症反应有关；然而，这一现象背后的具体分子机制尚未完全阐明。GrpE 是一种伴侣蛋白，可加速 ADP 释放和 ATP 与 DnaK 的结合，从而增强 HSP70 系统在压力下的伴侣功能。然而，人们对其替代活动（如促炎症反应）仍然知之甚少。在本研究中，我们报告了 U. urealyticum GrpE 作为细胞因子诱导毒力因子对巨噬细胞的作用。利用基因敲除小鼠和特异性抑制剂，我们发现 GrpE 诱导的促炎细胞因子表达是由 TLR2/STAT3 通路介导的。我们还发现，糖酵解对这种促炎反应至关重要。从机理上讲，GRPE 处理可刺激 STAT3 依赖性柠檬酸和乙酰-CoA 的积累，促进组蛋白乙酰化和强效促炎反应。我们的研究结果表明，糖酵解在 GrpE 通过 TLR2/STAT3 通路诱导的炎症反应中发挥作用，并促进了糖酵解介导的炎症反应，从而为尿囊炎感染的发展提供了新的认识。

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引用次数: 0

MAIT and iNKT cells in tissue homeostasis and repair MAIT和iNKT细胞在组织稳态和修复中的作用

IF 2.5 4区医学 Q3 IMMUNOLOGY

Immunobiology

Pub Date : 2025-05-01 Epub Date: 2025-05-22 DOI: 10.1016/j.imbio.2025.152917

Rafael Almeida Paiva , Marion Salou

Mucosal-associated invariant T (MAIT) and invariant natural killer T (iNKT) are innate-like T cells, which develop in the thymus through an original developmental program leading to the acquisition of effector memory and tissue targeting phenotypes. Consequently, they become tissue-resident and quickly produce effector molecules both in a T cell receptor (TCR)-dependent manner after stimulation by activating antigens, and in a TCR-independent fashion in response to cytokines. The latter can trigger MAIT and iNKT cells similarly, potentially leading to redundant functions. MAIT and iNKT cells populate most peripheral tissues where they express a wide range of effector modules including immune type 1/2/17, regulatory and repair programs. This endows them with a plethora of functional properties from anti-infectious immunity to regulation of homeostatic processes and tissue repair. In this review, we summarize the current literature on how MAIT and iNKT cells maintain organ homeostasis and contribute to regeneration in vivo, mostly focused on adipose tissue, intestine, lung, liver and skin. Furthermore, we underline TCR- and/or cytokine-dependent mechanisms and potential redundant, non-redundant or even opposing functions.

mucal -associated invariant T （MAIT）和invariant natural killer T （iNKT）是先天样T细胞，它们通过原始的发育程序在胸腺中发育，从而获得效应记忆和组织靶向表型。因此，它们成为组织驻留，并在激活抗原刺激后以T细胞受体（TCR）依赖的方式快速产生效应分子，以及在响应细胞因子时以TCR独立的方式产生效应分子。后者可以类似地触发MAIT和iNKT细胞，可能导致冗余功能。MAIT和iNKT细胞分布在大多数外周组织中，它们表达广泛的效应模块，包括免疫类型1/2/17，调节和修复程序。这使它们具有从抗感染免疫到调节体内平衡过程和组织修复的多种功能特性。在这篇综述中，我们总结了目前关于MAIT和iNKT细胞如何维持器官稳态和促进体内再生的文献，主要集中在脂肪组织、肠、肺、肝和皮肤。此外，我们强调了TCR和/或细胞因子依赖机制和潜在的冗余，非冗余甚至相反的功能。

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引用次数: 0

Decreased number of myeloid-derived suppressor cells in the placental trophoblast of gestational diabetes mellitus. Possible role of leptin 妊娠期糖尿病胎盘滋养细胞髓源性抑制细胞数量减少。瘦素的可能作用

IF 2.5 4区医学 Q3 IMMUNOLOGY

Immunobiology

Pub Date : 2025-05-01 Epub Date: 2025-03-25 DOI: 10.1016/j.imbio.2025.152897

Malika Tami , Lourdes Hontecillas-Prieto , Daniel García-Domínguez , Rocío Flores-Campos , Teresa Vilariño-García , Flora Sánchez-Jiménez , Pilar Guadix , José L. Dueñas , Carlos Jiménez-Cortegana , Luis de la Cruz-Merino , Antonio Pérez-Pérez , Víctor Sánchez-Margalet

Gestational diabetes mellitus (GDM) is the most common complication of pregnancy and significantly increases both maternal and fetal morbidity and mortality. Inflammation is a hallmark of GDM, and placental inflammation may play a key role in the pathophysiology of the disease. Myeloid-derived suppressor cells (MDSCs), which are innate immunosuppressive, are thought to contribute to feto-maternal tolerance. In normal pregnancies, elevated levels of MDSCs have been observed in both peripheral and umbilical cord blood. Our hypothesis postulates that trophoblasts from placentas belonging to women with GDM may have lower levels of MDSCs compared to trophoblasts from placentas originating from healthy pregnancies. Furthermore, since leptin is overexpressed in the placenta of GDM patients, we hypothesized that leptin might contribute to the reduction of MDSCs. To test this, we investigated the in vitro effects of leptin on MDSC levels in isolated peripheral blood leukocytes after 24 h of incubation. Our findings indicate that trophoblasts from placentas from women with GDM contain a lower percentage of MDSCs compared to trophoblasts from healthy pregnancies. In addition, in vitro studies demonstrated that leptin reduces the number of MDSCs in peripheral blood leukocytes.

In conclusion, MDSCs are decreased in placentas from pregnancies with GDM, and leptin appears to reduce the number of MDSCs in leukocytes isolated in vitro. Increased leptin expression in trophoblasts from placentas of women with GDM may contribute to the lower levels of MDSCs, potentially playing a role in placental inflammation. However, further investigations are required to fully elucidate this mechanism.

妊娠期糖尿病（GDM）是妊娠期最常见的并发症，显著增加母体和胎儿的发病率和死亡率。炎症是GDM的一个标志，胎盘炎症可能在该病的病理生理中起关键作用。骨髓源性抑制细胞（MDSCs）具有先天免疫抑制作用，被认为有助于胎儿对母体的耐受。在正常妊娠中，外周血和脐带血中均观察到MDSCs水平升高。我们的假设假设，来自GDM女性胎盘的滋养细胞与来自健康妊娠的胎盘的滋养细胞相比，可能具有更低水平的MDSCs。此外，由于瘦素在GDM患者的胎盘中过度表达，我们假设瘦素可能有助于MDSCs的减少。为了验证这一点，我们研究了瘦素在体外培养24小时后对分离外周血白细胞MDSC水平的影响。我们的研究结果表明，与健康妊娠的滋养细胞相比，来自GDM妇女胎盘的滋养细胞含有较低百分比的MDSCs。此外，体外研究表明，瘦素可减少外周血白细胞中MDSCs的数量。综上所述，妊娠期GDM的胎盘中MDSCs减少，瘦素似乎可以减少体外分离的白细胞中MDSCs的数量。GDM女性胎盘滋养细胞中瘦素表达增加可能导致MDSCs水平降低，可能在胎盘炎症中发挥作用。然而，需要进一步的研究来充分阐明这一机制。

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