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Targeting gut-brain-immune axis in amyotrophic lateral sclerosis. 肌萎缩性侧索硬化症的肠-脑-免疫轴靶向。
IF 5.9 2区 医学 Q1 IMMUNOLOGY Pub Date : 2026-01-29 eCollection Date: 2025-01-01 DOI: 10.3389/fimmu.2025.1637976
Naga Sriharsha Mudda, Lucas Zhang, Pooja Sampelli

Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron neurodegenerative disorder with a median survival of only 3-5 years. The heterogeneity of the disease and lack of effective therapies highlight the importance of identifying novel pathogenic mechanisms. We hypothesize that dysbiosis of gut microbiota enhances ALS by disrupting intestinal barrier function and altering metabolite profiles to drive systemic inflammation and neuronal stress. Precisely, the decrease in health-promoting bacteria (e.g., Akkermansia muciniphila, Bifidobacterium and Lactobacillus spp.) in ALS can reduce neuroprotective metabolite production (short-chain fatty acids, nicotinamide, GABA, precursors of serotonin) and increase gut permeability, enabling lipopolysaccharide (LPS) and pro-inflammatory cytokines into the circulation. Such changes would activate microglia and impair motor neuron homeostasis by glutamate excitotoxicity and mitochondrial dysfunction. The gut-brain axis operates through immune-mediated mechanisms, where ALS-associated microbiota changes compromise mucosal immunity and trigger peripheral Th1/Th17-biased responses with impaired Treg regulation. Elevated endotoxin levels correlate with TLR4-driven inflammation, promoting pro-inflammatory cytokines (IL-1β, IL-6, TNF-α) that cross into the CNS and prime microglia toward a neurotoxic M1 phenotype, creating a milieu where IL-17A and other mediators directly injure motor neurons. Our hypothesis relies on establishing human and animal evidence of microbiome derangements, barrier dysfunction, and immune deregulation with ALS. We hypothesize that restoration of an "ALS-protective" microbiota consortium or its metabolic by-products can potentially slow disease progression. Testable hypotheses include improvement of ALS model motor deficits by probiotic or fecal-microbiota therapies, and normalization of inflammatory biomarkers. This paradigm recontextualizes ALS as a gut-brain disease and suggests new directions for translational research into this unmet medical indication.

肌萎缩侧索硬化症(ALS)是一种致命的运动神经元神经退行性疾病,中位生存期仅为3-5年。该病的异质性和缺乏有效的治疗方法突出了确定新的致病机制的重要性。我们假设肠道菌群失调通过破坏肠道屏障功能和改变代谢物谱来驱动全身性炎症和神经元应激,从而增强ALS。确切地说,ALS中促进健康的细菌(如嗜粘杆菌、双歧杆菌和乳杆菌)的减少可以减少神经保护代谢物(短链脂肪酸、烟酰胺、GABA、血清素前体)的产生,增加肠道通透性,使脂多糖(LPS)和促炎细胞因子进入循环。这种变化会激活小胶质细胞,并通过谷氨酸兴奋毒性和线粒体功能障碍破坏运动神经元的稳态。肠脑轴通过免疫介导的机制运作,其中als相关的微生物群变化损害粘膜免疫并触发外周Th1/ th17偏倚反应,Treg调节受损。升高的内毒素水平与tlr4驱动的炎症相关,促进促炎细胞因子(IL-1β, IL-6, TNF-α)进入中枢神经系统和主要小胶质细胞,形成神经毒性M1表型,创造IL-17A和其他介质直接损伤运动神经元的环境。我们的假设依赖于建立微生物组紊乱、屏障功能障碍和免疫失调与ALS的人类和动物证据。我们假设,恢复“als保护”微生物群联合体或其代谢副产物可以潜在地减缓疾病进展。可测试的假设包括通过益生菌或粪便微生物群治疗改善ALS模型运动缺陷,以及炎症生物标志物的正常化。这一范式将ALS重新定位为一种肠-脑疾病,并为这一未满足的医学指征的转化研究提供了新的方向。
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引用次数: 0
Novel prognostic signature unveils PSEN1 contributes to depression-induced lung adenocarcinoma progression. 新的预后特征揭示PSEN1参与抑郁诱导的肺腺癌进展。
IF 5.9 2区 医学 Q1 IMMUNOLOGY Pub Date : 2026-01-29 eCollection Date: 2026-01-01 DOI: 10.3389/fimmu.2026.1681306
Qiaoqi Zheng, Ji Zhuoga, Congcong Li, Wenjing Chen, Maimaititusun Yalikun, Peng Fu, Zaiquan Dong, Jingcheng Dong

Purpose: Depression is acknowledged to correlate with the occurrence and progression of multiple cancers. However, no study has yet systematically complied depression-related genes to construct a prognostic signature for lung adenocarcinoma (LUAD).

Methods: Our study encompasses 1,276 LUAD patients from three cohorts. Consensus clustering was employed to classify patients into different depression subtypes. Then, a variety of machine-learning algorithms were utilized to construct a robust depression-related signature (DRS). Thereafter, a nomogram combining DRS with common clinical characteristics was established for prognosis. The IOBR package was used to quantify the immune landscape, whereas the oncoPredict and Connectivity Map algorithms were employed to evaluate therapeutic response. The Seurat package was applied to process single-cell data, and the Scissor algorithm was used to identify depression-associated cells. Ultimately, depression-like mouse models were constructed to detect alternations in depression-related genes. In vitro experiments were performed to explore the role of PSEN1 in the malignant behaviors of LUAD.

Results: Unsupervised clustering stratified patients into two subtypes with distinct features. DRS consisting of 14 hub depression-related genes was established using the LASSO + GBM algorithm and served as an independent prognostic indicator. The nomogram constructed with DRS demonstrated robust predictive efficacy, with a C-index of 0.778. LUAD patients in the high-risk group exhibited weaker "immune hot" features and reduced responsiveness to immunotherapy. Additionally, high-risk patients were less sensitive to conventional chemotherapy and targeted therapies. Single-cell analysis revealed that depression-associated high-risk cells displayed more malignant characteristics. Finally, qRT-PCR validated the alternations of depression-related genes in depression-like mouse models, and in vitro experiments confirmed that PSEN1 facilitated cell proliferation in LUAD.

Conclusions: The molecular profile defined by the DRS can serve as an independent overall survival predictor and improve individualized treatment and clinical decision for LUAD patients. Of which, PSEN1 may contribute to depression-induced LUAD progression.

目的:抑郁症被认为与多种癌症的发生和发展有关。然而,目前还没有研究系统地收集抑郁相关基因来构建肺腺癌(LUAD)的预后特征。方法:我们的研究包括来自三个队列的1,276例LUAD患者。采用共识聚类法将患者分为不同的抑郁亚型。然后,利用各种机器学习算法构建鲁棒抑郁相关签名(DRS)。然后,将DRS与常见的临床特征相结合,建立一种预测预后的nomogram。IOBR包被用来量化免疫景观,而oncoPredict和连通性地图算法被用来评估治疗反应。Seurat软件包用于处理单细胞数据,Scissor算法用于识别抑郁症相关细胞。最终,构建了抑郁症样小鼠模型,以检测抑郁症相关基因的变化。通过体外实验探讨PSEN1在LUAD恶性行为中的作用。结果:无监督聚类将患者分为两个具有不同特征的亚型。采用LASSO + GBM算法建立由14个中枢抑郁相关基因组成的DRS,作为独立的预后指标。采用DRS构建的nomogram具有较强的预测效果,C-index为0.778。高危组LUAD患者表现出较弱的“免疫热”特征,对免疫治疗的反应性降低。此外,高危患者对常规化疗和靶向治疗的敏感性较低。单细胞分析显示,与抑郁相关的高危细胞表现出更多的恶性特征。最后,qRT-PCR验证了抑郁样小鼠模型中抑郁相关基因的改变,体外实验证实PSEN1促进LUAD细胞增殖。结论:DRS定义的分子谱可作为独立的总生存预测指标,改善LUAD患者的个体化治疗和临床决策。其中,PSEN1可能促进抑郁诱导的LUAD进展。
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引用次数: 0
Enhanced CHI3L1 promotes macrophage activation in persistent inflammatory events of ulcerative interstitial cystitis. 增强的CHI3L1促进巨噬细胞在溃疡性间质性膀胱炎持续炎症事件中的激活。
IF 5.9 2区 医学 Q1 IMMUNOLOGY Pub Date : 2026-01-29 eCollection Date: 2026-01-01 DOI: 10.3389/fimmu.2026.1716297
Wei Zhang, Yize Guo, Jiawen Wang, Xiaodong Liu, Ting Xie, Yao Li

Background: Interstitial cystitis/bladder pain syndrome (IC/BPS), particularly the Hunner-type subtype (HIC), is a chronic inflammatory bladder disorder characterized by persistent inflammation and macrophage-driven immunometabolic dysregulation. CHI3L1, a secreted glycoprotein implicated in inflammation and tissue remodeling, is significantly upregulated in HIC and correlates with disease severity, but its mechanistic role in macrophage-mediated persistent inflammatory events (PIEs) remains poorly defined.

Methods: This study integrated multi-omics analyses, including bioinformatics of IC/BPS transcriptomic datasets, a cyclophosphamide-induced IC/BPS mouse model for in vivo validation, and in vitro functional assays involving CHI3L1 overexpression in macrophages. Transcriptomic, metabolomic, and molecular biology techniques were employed to evaluate metabolic shifts, inflammatory pathways, and transcription factor correlations.

Results: CHI3L1 expression was significantly upregulated in HIC patients, especially those with reduced bladder capacity, and correlated with inflammatory markers (IL-6, TNFα). In macrophages, CHI3L1 overexpression drove pro-inflammatory activation via NF-κB and TNF pathways, promoted glycolysis, and suppressed mitochondrial oxidative phosphorylation (OXPHOS) and aspartate metabolism. Critically, CHI3L1 expression strongly correlated with the transcription factor MYC rather than STAT3 under inflammatory conditions, reinforcing M1 polarization.

Conclusions: CHI3L1 exacerbates PIEs in HIC by reprogramming macrophage metabolism toward glycolysis and sustaining inflammation via MYC signaling. These findings establish CHI3L1 as a central regulator of chronic inflammation in HIC and highlight its potential as a therapeutic target for disrupting pathological immune-metabolic cycles.

背景:间质性膀胱炎/膀胱疼痛综合征(IC/BPS),特别是hunner亚型(HIC),是一种慢性炎性膀胱疾病,其特征是持续炎症和巨噬细胞驱动的免疫代谢失调。CHI3L1是一种参与炎症和组织重塑的分泌糖蛋白,在HIC中显著上调,并与疾病严重程度相关,但其在巨噬细胞介导的持续性炎症事件(PIEs)中的机制作用仍不清楚。方法:本研究整合了多组学分析,包括IC/BPS转录组数据集的生物信息学,环磷酰胺诱导的IC/BPS小鼠模型的体内验证,以及巨噬细胞中CHI3L1过表达的体外功能分析。转录组学、代谢组学和分子生物学技术被用来评估代谢变化、炎症途径和转录因子的相关性。结果:ch3l1表达在HIC患者中显著上调,尤其是膀胱容量减少患者,且与炎症标志物(IL-6、TNFα)相关。在巨噬细胞中,CHI3L1过表达通过NF-κB和TNF途径激活促炎,促进糖酵解,抑制线粒体氧化磷酸化(OXPHOS)和天冬氨酸代谢。关键的是,在炎症条件下,CHI3L1的表达与转录因子MYC而不是STAT3密切相关,从而加强了M1极化。结论:CHI3L1通过将巨噬细胞代谢重编程为糖酵解和通过MYC信号维持炎症,从而加剧HIC中的pie。这些发现证实了CHI3L1是HIC慢性炎症的中心调节因子,并强调了其作为破坏病理性免疫代谢周期的治疗靶点的潜力。
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引用次数: 0
Myeloid-derived suppressor cells and regulatory T cells in colorectal cancer: a synergistic immunosuppressive axis and emerging therapeutic opportunities. 结直肠癌中的骨髓源性抑制细胞和调节性T细胞:协同免疫抑制轴和新兴治疗机会。
IF 5.9 2区 医学 Q1 IMMUNOLOGY Pub Date : 2026-01-29 eCollection Date: 2026-01-01 DOI: 10.3389/fimmu.2026.1757513
Wenxing Zhang, Chenrui Jin, Shuyuan Liu, Xing Wan, Yu Li, Jifeng Liu, Zhijun Duan, Jingyuan Ma, Yunhai Gao

Microsatellite-stable (MSS)/proficient mismatch-repair (pMMR) colorectal cancer (CRC) accounts for more than 85% of cases but responds poorly to single-agent immune checkpoint inhibitors (ICIs), with objective response rates remaining below 5%. A principal barrier to effective immunotherapy in these tumors is a durable immunosuppressive axis formed by myeloid-derived suppressor cells (MDSCs) and regulatory T cells (Tregs) within the tumor microenvironment. This axis impedes antitumor immunity through multilayered mechanisms including bidirectional chemotactic recruitment, reciprocal cytokine signaling, metabolic suppression and exosome-mediated communication. CRC is uniquely influenced by the gut microbiota: Fusobacterium nucleatum promotes MDSC/Treg enrichment via TLR4-NF-κB and Fap2-TIGIT pathways; Peptostreptococcus anaerobius acts through integrin-PI3K-NF-κB signaling; and microbial metabolites such as 4-HPA activate JAK2/STAT3-CXCL3 signaling to expand MDSC populations. Concurrently, a hypoxia-lactate-HIF-1α-CD73/A2AR circuit further stabilizes suppressive phenotypes, forming a "microbiota-metabolism-hypoxia-MDSC-Treg" cascade. Emerging clinical and translational data indicate that disrupting this axis can sensitize MSS-CRC to ICIs: for example, Zanzalintinib combined with Atezolizumab reported survival benefit in the STELLAR-303 trial, and dual blockade of novel checkpoints with PD-(L)1 has been associated with enhanced immune activation in solid tumors. Targeting the MDSC-Treg axis therefore represents a promising strategy to overcome immunotherapy resistance in MSS/pMMR CRC.

微卫星稳定型(MSS)/熟练错配修复型(pMMR)结直肠癌(CRC)占85%以上的病例,但对单药免疫检查点抑制剂(ICIs)的反应较差,客观反应率仍低于5%。这些肿瘤有效免疫治疗的主要障碍是由肿瘤微环境中的髓源性抑制细胞(MDSCs)和调节性T细胞(Tregs)形成的持久免疫抑制轴。该轴通过多层机制阻碍抗肿瘤免疫,包括双向趋化募集、相互细胞因子信号传导、代谢抑制和外泌体介导的通讯。结直肠癌受肠道菌群的独特影响:核梭杆菌通过TLR4-NF-κB和Fap2-TIGIT途径促进MDSC/Treg富集;厌氧胃链球菌通过整合素- pi3k - nf -κB信号传导起作用;微生物代谢物如4-HPA激活JAK2/STAT3-CXCL3信号,扩大MDSC种群。同时,缺氧-乳酸- hif -1α- cd73 /A2AR回路进一步稳定了抑制表型,形成了“微生物-代谢-缺氧- mdsc - treg”级联。新出现的临床和转化数据表明,破坏该轴可使MSS-CRC对ICIs敏感:例如,在stelar -303试验中,zanzalinib联合Atezolizumab报告了生存获益,并且PD-(L)1双重阻断新检查点与实体肿瘤中增强的免疫激活有关。因此,靶向MDSC-Treg轴代表了一种克服MSS/pMMR CRC免疫治疗耐药的有希望的策略。
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引用次数: 0
Artemisinin exerts anti-inflammatory effects in osteoarthritis through the inhibition of TGF-β1 signaling. 青蒿素通过抑制TGF-β1信号通路在骨关节炎中发挥抗炎作用。
IF 5.9 2区 医学 Q1 IMMUNOLOGY Pub Date : 2026-01-29 eCollection Date: 2026-01-01 DOI: 10.3389/fimmu.2026.1717045
Xifan Zheng, Bo Yu, Yuansong Song, Yeping Chen, Zeming Li, Jun Yao

Objective: Osteoarthritis (OA) involves an inflammatory imbalance, yet key mediators and their interplay with potential therapeutics like artemisinin (ART) remain poorly understood. This study aimed to systematically investigate these relationships using Mendelian randomization and to decipher their functional interactions through cellular and molecular experiments, complemented by network pharmacology and molecular docking analyses.

Methods: Using the Mendelian randomization (MR) method, we integrated independent exposure-outcome genome-wide association study data to evaluate the causal association between inflammatory cytokines and OA. Chondrocytes were treated with IL-1β, TGF-β1 (5 μg/mL), and ART (4 μg/mL) for 24 hours. Cell proliferation was assessed using CCK-8 and EdU assays, and gene/protein expression was analyzed via RT-qPCR, Western blotting, and immunofluorescence staining. In parallel, network pharmacology was performed to identify putative ART targets related to OA and to characterize enriched pathways and hub genes through GO/KEGG enrichment and protein-protein interaction (PPI) analyses. Molecular docking was further conducted to evaluate the binding feasibility between ART and the catabolic mediator MMP-13.

Results: MR revealed a positive association between TGF-β1 and OA risk (OR = 1.0526, P = 0.0182). Functionally, ART significantly enhanced chondrocyte proliferation, whereas TGF-β1 inhibited it. ART downregulated IL-1β and MMP13 expression, while TGF-β1 upregulated them, indicating opposing effects in OA chondrocytes. Network pharmacology suggested that ART-related OA targets were enriched in inflammation-associated processes and signaling pathways (e.g., MAPK signaling), with PPI analysis highlighting inflammatory signaling hubs (e.g., JAK/STAT-related nodes). Consistently, molecular docking demonstrated favorable binding of ART within the MMP-13 active pocket, supporting the structural feasibility of an ART-MMP-13 interaction.

Conclusion: This study demonstrates that TGF-β1 plays an important pathogenic role in OA, as supported by MR and in vitro evidence, while ART exhibits anti-inflammatory and anti-catabolic effects by counteracting TGF-β1-driven inflammatory responses. Network pharmacology and docking analyses further suggest multi-target pathway regulation and a potential interaction with MMP-13. ART may represent a viable therapeutic candidate for OA; however, further studies are required to validate direct targets and elucidate tissue-specific mechanisms.

目的:骨关节炎(OA)涉及炎症失衡,但关键介质及其与潜在治疗药物(如青蒿素(ART))的相互作用仍知之甚少。本研究旨在利用孟德尔随机化系统地研究这些关系,并通过细胞和分子实验,辅以网络药理学和分子对接分析,破译它们之间的功能相互作用。方法:使用孟德尔随机化(MR)方法,我们整合了独立的暴露-结局全基因组关联研究数据,以评估炎症细胞因子与OA之间的因果关系。用IL-1β、TGF-β1 (5 μg/mL)、ART (4 μg/mL)处理软骨细胞24小时。采用CCK-8和EdU检测细胞增殖,RT-qPCR、Western blotting和免疫荧光染色检测基因/蛋白表达。与此同时,通过GO/KEGG富集和蛋白-蛋白相互作用(PPI)分析,我们进行了网络药理学研究,以确定与OA相关的可能的ART靶点,并表征富集的途径和枢纽基因。进一步进行分子对接,评估ART与分解代谢介质MMP-13结合的可行性。结果:MR显示TGF-β1与OA风险呈正相关(OR = 1.0526, P = 0.0182)。在功能上,ART显著促进软骨细胞增殖,而TGF-β1则抑制其增殖。ART下调IL-1β和MMP13的表达,而TGF-β1上调它们的表达,在OA软骨细胞中显示相反的作用。网络药理学提示,art相关的OA靶点在炎症相关过程和信号通路(如MAPK信号)中富集,PPI分析突出炎症信号中枢(如JAK/ stat相关节点)。一致地,分子对接显示ART在MMP-13活性口袋内的良好结合,支持ART-MMP-13相互作用的结构可行性。结论:本研究证实TGF-β1在OA中具有重要的致病作用,MR和体外证据均支持,而ART通过对抗TGF-β1驱动的炎症反应发挥抗炎和抗分解代谢作用。网络药理学和对接分析进一步表明多靶点通路调控和与MMP-13的潜在相互作用。ART可能是OA的一种可行的治疗方案;然而,需要进一步的研究来验证直接靶点和阐明组织特异性机制。
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引用次数: 0
Immune cell dynamics and mechanisms of epithelial injury in celiac disease. 乳糜泻中上皮损伤的免疫细胞动力学和机制。
IF 5.9 2区 医学 Q1 IMMUNOLOGY Pub Date : 2026-01-29 eCollection Date: 2026-01-01 DOI: 10.3389/fimmu.2026.1766513
Irene Marafini, Silvia Salvatori, Edoardo Troncone, Pasquale De Vico, Elena De Cristofaro, Giovanni Monteleone

Despite continuous exposure to dietary and microbial antigens, the intestinal mucosa maintains a delicate balance between immune activation and tolerance. This equilibrium depends on the integrity and regulatory functions of the intestinal epithelium and associated immune cells. In the case of celiac disease (CD), gluten ingestion disturbs this equilibrium in people with a genetic predisposition (those with HLA-DQ2 or HLA-DQ8 alleles), and this results in chronic inflammation and villous atrophy. Tissue transglutaminase 2 (TG2) modifies gluten peptides, thus enhancing their affinity for HLA-DQ2/8, with the downstream effect of triggering CD4+ T cell-mediated Th1 responses dominated by IFN-γ and IL-21. The same cytokines along with IL-15, which is released by the epithelial and dendritic cells, stimulate the activation of cytotoxic intraepithelial lymphocytes that, in turn, kill enterocytes. Additional innate pathways, including those induced by gliadin-derived peptides, α-amylase/trypsin inhibitors, and type I interferons, further amplify epithelial stress and immune activation. Crosstalk between immune and stromal cells and defects in counterregulatory mechanisms contribute to persistent tissue injury. Emerging evidence implicates the gut microbiota in modulating both gluten-dependent and -independent immune responses through protease activity and barrier regulation. We here review the available evidence supporting the role of immune cells in CD-associated tissue damage and discuss the basic mechanisms by which this destructive immune response is amplified.

尽管持续暴露于饮食和微生物抗原,肠黏膜维持免疫激活和耐受性之间的微妙平衡。这种平衡依赖于肠上皮和相关免疫细胞的完整性和调节功能。在乳糜泻(CD)的情况下,麸质摄入扰乱了遗传易感性人群(HLA-DQ2或HLA-DQ8等位基因)的这种平衡,这导致慢性炎症和绒毛萎缩。组织转谷氨酰胺酶2 (TG2)修饰谷蛋白肽,从而增强其对HLA-DQ2/8的亲和力,其下游作用是触发CD4+ T细胞介导的由IFN-γ和IL-21主导的Th1反应。同样的细胞因子和由上皮细胞和树突状细胞释放的IL-15一起,刺激细胞毒性上皮内淋巴细胞的激活,进而杀死肠细胞。其他先天通路,包括麦胶蛋白衍生肽、α-淀粉酶/胰蛋白酶抑制剂和I型干扰素诱导的通路,进一步放大了上皮应激和免疫激活。免疫细胞和基质细胞之间的串扰以及反调节机制的缺陷导致了持续的组织损伤。新出现的证据表明,肠道微生物群通过蛋白酶活性和屏障调节调节麸质依赖性和非依赖性免疫反应。本文回顾了支持免疫细胞在cd相关组织损伤中的作用的现有证据,并讨论了这种破坏性免疫反应被放大的基本机制。
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引用次数: 0
Cytokines in patients with Posner-Schlossman syndrome. Posner-Schlossman综合征患者的细胞因子。
IF 5.9 2区 医学 Q1 IMMUNOLOGY Pub Date : 2026-01-29 eCollection Date: 2026-01-01 DOI: 10.3389/fimmu.2026.1739027
Yu Liu, Shengjie Li, Xiangmei Kong, Qilian Sheng, Zhujian Wang, Wenjun Cao

Purpose: To investigate the inflammatory cytokine profiles in the aqueous humor (AH) of patients with Posner-Schlossman syndrome (PSS) and evaluate their correlations with key ophthalmic parameters.

Methods: Aqueous humor samples were collected from 31 eyes with PSS, 26 eyes with primary open-angle glaucoma (POAG), and 20 eyes with age-related cataract (ARC, control group) at the Eye and ENT Hospital of Fudan University. A multiplex bead-based flow cytometric immunoassay was performed to quantify the concentrations of interleukins (IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, IL-17), tumor necrosis factor-alpha (TNF-α), and interferons (IFN-α, IFN-γ). Simultaneously, the presence of cytomegalovirus (CMV) DNA in PSS samples was assessed by PCR. Clinical data including corneal endothelial cell density, visual acuity, intraocular pressure (IOP), and visual field were also recorded.

Results: The AH levels of IL-1β, IL-5, IL-6, IL-8, IL-10, IFN-γ, and TNF-α were significantly elevated in PSS patients compared to controls (P < 0.05), with IL-1β, IL-6, IL-10, and IFN-γ levels also significantly higher than in POAG patients. ROC curve analysis demonstrated diagnostic value of these four cytokines in differentiating PSS from POAG (P<0.05). No significant differences in cytokine levels were observed between CMV DNA-positive and -negative PSS samples. Notably, IL-6 levels positively correlated with IL-8 and IL-10, and also showed significant associations with IOP (r = 0.395, P = 0.007) and relative endothelial cell loss (RECL) (r = 0.453, P = 0.039).

Conclusion: Distinct inflammatory cytokine profiles in the AH of PSS patients suggest a prominent immune response potentially contributing to disease pathogenesis. IL-6 may serve as a biomarker reflecting both inflammation and tissue damage in PSS. Note: CECD, corneal endothelial cell density; RECL, relative decrease in CECD loss between the affected eye and the fellow eye.

目的:探讨Posner-Schlossman综合征(PSS)患者房水(AH)中炎症细胞因子的变化及其与关键眼科参数的相关性。方法:选取复旦大学眼科耳鼻喉科医院31眼PSS、26眼原发性开角型青光眼(POAG)和20眼老年性白内障(ARC,对照组)的房水标本。采用基于多重球的流式细胞免疫分析法定量白细胞介素(IL-1β、IL-2、IL-4、IL-5、IL-6、IL-8、IL-10、IL-12、IL-17)、肿瘤坏死因子-α (TNF-α)和干扰素(IFN-α、IFN-γ)的浓度。同时,用PCR方法检测PSS标本中巨细胞病毒(CMV) DNA的存在。临床数据包括角膜内皮细胞密度、视力、眼压、视野等。结果:PSS患者AH中IL-1β、IL-5、IL-6、IL-8、IL-10、IFN-γ、TNF-α水平显著高于对照组(P < 0.05), IL-1β、IL-6、IL-10、IFN-γ水平也显著高于POAG患者。ROC曲线分析证明了这四种细胞因子在区分PSS和POAG方面的诊断价值。结论:PSS患者AH中不同的炎症细胞因子谱表明,一种突出的免疫反应可能有助于疾病的发病机制。IL-6可能是反映PSS炎症和组织损伤的生物标志物。注:ced,角膜内皮细胞密度;RECL,受累眼与同侧眼之间ced损失的相对减少。
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引用次数: 0
Orchestrating immunopathology: the spectrum of programmed cell death pathways co-opted by influenza a virus in pulmonary immunity. 协调免疫病理:甲型流感病毒在肺免疫中选择的程序性细胞死亡途径的频谱。
IF 5.9 2区 医学 Q1 IMMUNOLOGY Pub Date : 2026-01-29 eCollection Date: 2026-01-01 DOI: 10.3389/fimmu.2026.1705500
Yuanyuan Luo, Li Xiang, Qingman He, Yongxiang Gao, Chuan Zheng, Huan Yao

Influenza A virus (IAV) infection activates multiple programmed cell death (PCD) pathways, which, while restricting viral replication and dissemination, concurrently disrupt the respiratory epithelial barrier and compromise immune homeostasis. Excessive activation of apoptosis, necroptosis, pyroptosis, and related processes results in tight junction(TJ) disruption, impaired mucociliary clearance and gas exchange, and amplification of inflammatory cascades, ultimately driving cytokine storm and severe tissue injury. This dual role of PCD underscores its importance in antiviral defense while exposing its potential to exacerbate immunopathology. Accordingly, this review focuses on IAV-induced PCD mechanisms, delineating their contribution to epithelial barrier breakdown and immune dysregulation, with the aim of informing strategies for precise modulation of immunopathological damage and improving therapeutic outcomes in severe influenza.

甲型流感病毒(IAV)感染激活了多个程序性细胞死亡(PCD)途径,这在限制病毒复制和传播的同时,也破坏了呼吸道上皮屏障并破坏了免疫稳态。细胞凋亡、坏死、焦亡及其相关过程的过度激活导致紧密连接(TJ)破坏,粘膜纤毛清除和气体交换受损,炎症级联扩增,最终导致细胞因子风暴和严重的组织损伤。PCD的双重作用强调了其在抗病毒防御中的重要性,同时暴露了其加剧免疫病理的潜力。因此,本文将重点关注iav诱导的PCD机制,描述其对上皮屏障破坏和免疫失调的贡献,目的是为精确调节免疫病理损伤和改善严重流感的治疗效果提供策略。
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引用次数: 0
Case Report: CAR-T cell therapy bridging to allogeneic hematopoietic stem cell transplantation triggers Purtscher-like retinopathy: clinical features and complement-mediated microvascular injury mechanisms. 病例报告:CAR-T细胞治疗桥接异体造血干细胞移植引发purtscher样视网膜病变:临床特征和补体介导的微血管损伤机制
IF 5.9 2区 医学 Q1 IMMUNOLOGY Pub Date : 2026-01-29 eCollection Date: 2026-01-01 DOI: 10.3389/fimmu.2026.1670399
Zhihui Li, Tao Zhang, Qian Fei, Xianxuan Wang, Jing Li, Yong Tao, Tong Wu

Purtscher-like retinopathy (PLR) is a secondary, non-traumatic occlusive microvascular retinal disease characterized by retinal leukoderma, hemorrhage, and cotton wool spots. It is commonly associated with conditions such as pancreatitis, renal disease, and infections including COVID-19 but is rarely reported in patients with hematologic malignancies, particularly following hematopoietic stem cell transplantation (HSCT). This article reports a case of relapsed B-cell acute lymphoblastic leukemia (B-ALL) in a patient who underwent multiple lines of immunotherapy, including CD19- and CD22-targeted CAR-T cells, inotuzumab ozogamicin (an anti-CD22 antibody-drug conjugate), and belimumab (a CD19/CD3 bispecific T-cell engager), followed by allogeneic HSCT from an unrelated donor. Early post-transplantation, an influenza A (H1N1) infection likely triggered the onset of PLR. On post-transplant day 160, the patient presented with sudden, painless vision loss in the left eye. Fundoscopic examination revealed retinal hemorrhages, Purtscher flecken, and macular edema, confirming the diagnosis of PLR. By day 194, new-onset thrombocytopenia, proteinuria, and progressively elevated serum creatinine levels suggested an association between PLR and transplant-associated thrombotic microangiopathy (TA-TMA). This case illustrates that multi-agent immunotherapy prior to HSCT for acute leukemia may cause cumulative endothelial injury and that influenza A infection can act as a trigger for PLR in the post-HSCT setting. Early recognition and management of PLR and TA-TMA could improve clinical outcomes. Consequently, close monitoring for these complications is essential in post-transplant patients, particularly those with a history of intensive immunotherapy or subsequent viral infection. Implementing a "systemic-local" endothelial monitoring framework may facilitate timely intervention and enhance patient prognosis.

Purtscher-like retinopathy (PLR)是一种继发性、非外伤性闭塞性微血管视网膜疾病,其特征为视网膜白皮、出血和棉毛斑。它通常与胰腺炎、肾脏疾病和感染(包括COVID-19)等疾病有关,但很少在血液恶性肿瘤患者中报道,特别是在造血干细胞移植(HSCT)后。本文报道了一例复发的b细胞急性淋巴细胞白血病(B-ALL)患者,他接受了多种免疫治疗,包括靶向CD19和cd22的CAR-T细胞,inotuzumab ozogamicin(一种抗cd22抗体-药物偶联物)和belimumab(一种CD19/CD3双特异性t细胞结合物),随后接受了来自非相关供体的同种异体造血干细胞移植。移植后早期,甲型H1N1流感感染可能引发了PLR的发病。移植后第160天,患者出现左眼突然无痛性视力丧失。眼底镜检查发现视网膜出血、斑疹、黄斑水肿,证实了PLR的诊断。第194天,新发血小板减少症、蛋白尿和逐渐升高的血清肌酐水平提示PLR与移植相关血栓性微血管病变(TA-TMA)之间存在关联。该病例表明,急性白血病移植前的多药免疫治疗可能会引起累积的内皮损伤,甲型流感感染可能是移植后PLR的触发因素。早期识别和处理PLR和TA-TMA可改善临床预后。因此,密切监测这些并发症对移植后患者至关重要,特别是那些有强化免疫治疗史或随后的病毒感染的患者。实施“系统-局部”内皮监测框架可促进及时干预并提高患者预后。
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引用次数: 0
Human amnion epithelial cells induce M2 macrophage polarisation partially via M-CSF secretion but independently of extracellular vesicles in vitro. 人羊膜上皮细胞在体外部分通过M-CSF分泌诱导M2巨噬细胞极化,但不依赖于细胞外囊泡。
IF 5.9 2区 医学 Q1 IMMUNOLOGY Pub Date : 2026-01-29 eCollection Date: 2026-01-01 DOI: 10.3389/fimmu.2026.1723968
Louise Zeijlon, Snehil Budhwar, Robert Lindau, Stefan Bencina, Helen Kaipe, Maria C Jenmalm, Roberto Gramignoli, Johanna Raffetseder

Pregnancy requires major immunomodulatory changes, both systemically and locally, as the maternal immune system needs to be modulated to tolerate the semi-allogeneic foetus. Decidual macrophages and stromal cells, but also foetal tissues are involved in this immune tolerance, for example by inducing M2 macrophages and regulatory T cells. However, it is so far unknown whether foetal membrane cells such as amnion epithelial cells (AECs) can influence human macrophage polarisation. In this study, a human in vitro macrophage assay was employed to demonstrate that conditioned medium (CM) from AECs derived from term placentas induces M2 macrophage polarisation, and to compare AEC culture conditions aiming for efficient M2 polarisation. Macrophage colony-stimulating factor (M-CSF), a well-known M2-inducing cytokine, was found to be secreted by AECs, and M-CSF was partly responsible for the observed M2-polarising effect of AECs. In addition, the M2-polarising effect remained after removal of extracellular vesicles (EVs) from AEC-CM, suggesting the involvement of soluble but not of EV-associated mediators. Taken together, this study shows that AECs may contribute to the induction of the vital immunotolerant environment at the foetal-maternal interface. Based on their immunomodulatory effects observed here and in in vivo studies, AECs could be harnessed as cytotherapeutics for inflammatory disorders.

怀孕需要全身和局部的重大免疫调节变化,因为母体免疫系统需要调节以耐受半异体胎儿。蜕膜巨噬细胞和基质细胞,以及胎儿组织都参与了这种免疫耐受,例如通过诱导M2巨噬细胞和调节性T细胞。然而,胎儿膜细胞如羊膜上皮细胞(AECs)是否能影响人巨噬细胞极化目前尚不清楚。本研究采用人体外巨噬细胞实验证明,来自足月胎盘的AEC的条件培养基(CM)可诱导M2巨噬细胞极化,并比较AEC培养条件,以达到有效的M2极化。巨噬细胞集落刺激因子(Macrophage colony-stimulating factor, M-CSF)是一种众所周知的诱导m2的细胞因子,AECs分泌巨噬细胞集落刺激因子(Macrophage colony-stimulating factor, M-CSF), M-CSF是AECs产生m2极化效应的部分原因。此外,从AEC-CM中去除细胞外囊泡(EVs)后,m2极化效应仍然存在,表明可溶介质参与其中,而不是EVs相关介质。综上所述,本研究表明aec可能有助于在胎儿-母体界面诱导重要的免疫耐受环境。基于在这里和体内研究中观察到的免疫调节作用,AECs可以作为炎症疾病的细胞治疗药物。
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引用次数: 0
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Frontiers in Immunology
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