Journal of neuroimmunology最新文献_第5页

Modulation of inflammatory and regenerative responses by Galectin-3 after spinal cord injury in wild-type and Galectin-3 knockout mice 半乳糖凝集素-3在野生型和半乳糖凝集素-3敲除小鼠脊髓损伤后炎症和再生反应的调节。

IF 2.5 4区医学 Q3 IMMUNOLOGY

Journal of neuroimmunology

Pub Date : 2025-11-21 DOI: 10.1016/j.jneuroim.2025.578818

Emanuela Bezerra dos Santos Ribeiro , Luiza dos Santos Heringer , Bruna dos Santos Ramalho , Tiago Bastos Taboada , Fernanda Martins de Almeida , Ana Maria Blanco Martinez

Spinal cord injury (SCI) occurs either after a sudden trauma or through a chronic process at segmental levels of the spinal cord, leading to potentially deleterious neural consequences for the central nervous system (CNS) due to the death of neurons, oligodendrocytes, and astrocytes, as well as significant losses in motor, sensory, and autonomic functions. After SCI, an inflammatory response occurs, with cells such as macrophages and microglia being recruited. These cells are responsible for removing damaged tissue and secreting pro-inflammatory and anti-inflammatory cytokines and chemokines. Additionally, a protein called galectin-3 has been described as participating in cell activation, proliferation, and migration, acting as a mediator of inflammation in neurodegeneration. Thus, different populations of inflammatory cells in the injured nervous parenchyma can be characterized. In this study, we used a spinal cord contusion-compression model in wild-type C57Bl/6 mice (WT) and galectin-3 knockout mice (GAL3−/−) to histologically characterize the lesion, focusing on astrocyte, macrophage, and microglial populations. Our results showed a significant reduction in lesion propagation in GAL3−/− animals compared to WT animals. Moreover, GAL3−/− animals exhibited reduced astrogliosis compared to WT animals. Immunohistochemistry revealed that GAL3−/− animals had a larger area marked for the anti-inflammatory marker Arginase-1 and a smaller area marked for the pro-inflammatory marker iNOS compared to WT animals. We conclude that galectin-3 plays a critical role in the inflammatory process following spinal cord injury, and its absence may contribute to reduced lesion progression, decreased astrogliosis, and the promotion of an inflammatory response with a more anti-inflammatory profile.

Significance statement

This study highlights galectin-3 as a central mediator of the inflammatory response after spinal cord injury, demonstrating that galectin-3 deficiency limits lesion progression, attenuates astrogliosis, and promotes an anti-inflammatory profile. Thus, galectin-3 may represent a promising potential therapeutic target for clinical applications in neurodegenerative diseases.

脊髓损伤（SCI）发生于脊髓节段性水平的突然创伤或慢性过程，由于神经元、少突胶质细胞和星形胶质细胞的死亡，以及运动、感觉和自主神经功能的显著丧失，对中枢神经系统（CNS）造成潜在的有害神经后果。脊髓损伤后，炎症反应发生，巨噬细胞和小胶质细胞等细胞被招募。这些细胞负责清除受损组织，分泌促炎和抗炎细胞因子和趋化因子。此外，一种被称为半乳糖凝集素-3的蛋白质被描述为参与细胞活化、增殖和迁移，作为神经变性炎症的介质。因此，不同群体的炎症细胞损伤的神经实质可以表征。在这项研究中，我们使用野生型C57Bl/6小鼠（WT）和半乳糖凝集素-3敲除小鼠（GAL3-/-）的脊髓损伤压缩模型对病变进行组织学表征，重点关注星形胶质细胞、巨噬细胞和小胶质细胞群。我们的研究结果显示，与WT动物相比，GAL3-/-动物的病变增殖显著减少。此外，与WT动物相比，GAL3-/-动物表现出星形胶质细胞增生减少。免疫组化结果显示，与WT动物相比，GAL3-/-动物的抗炎标志物Arginase-1标记面积更大，促炎标志物iNOS标记面积更小。我们得出结论，半乳糖凝集素-3在脊髓损伤后的炎症过程中起关键作用，其缺失可能有助于减少病变进展，减少星形胶质细胞形成，并促进炎症反应，具有更强的抗炎特征。意义声明：这项研究强调了半乳糖凝集素-3作为脊髓损伤后炎症反应的中心介质，表明半乳糖凝集素-3缺乏限制了病变进展，减轻了星形胶质细胞增生，并促进了抗炎作用。因此，半乳糖凝集素-3可能是神经退行性疾病临床应用的潜在治疗靶点。

{"title":"Modulation of inflammatory and regenerative responses by Galectin-3 after spinal cord injury in wild-type and Galectin-3 knockout mice","authors":"Emanuela Bezerra dos Santos Ribeiro , Luiza dos Santos Heringer , Bruna dos Santos Ramalho , Tiago Bastos Taboada , Fernanda Martins de Almeida , Ana Maria Blanco Martinez","doi":"10.1016/j.jneuroim.2025.578818","DOIUrl":"10.1016/j.jneuroim.2025.578818","url":null,"abstract":"<div><div>Spinal cord injury (SCI) occurs either after a sudden trauma or through a chronic process at segmental levels of the spinal cord, leading to potentially deleterious neural consequences for the central nervous system (CNS) due to the death of neurons, oligodendrocytes, and astrocytes, as well as significant losses in motor, sensory, and autonomic functions. After SCI, an inflammatory response occurs, with cells such as macrophages and microglia being recruited. These cells are responsible for removing damaged tissue and secreting pro-inflammatory and anti-inflammatory cytokines and chemokines. Additionally, a protein called galectin-3 has been described as participating in cell activation, proliferation, and migration, acting as a mediator of inflammation in neurodegeneration. Thus, different populations of inflammatory cells in the injured nervous parenchyma can be characterized. In this study, we used a spinal cord contusion-compression model in wild-type C57Bl/6 mice (WT) and galectin-3 knockout mice (GAL3−/−) to histologically characterize the lesion, focusing on astrocyte, macrophage, and microglial populations. Our results showed a significant reduction in lesion propagation in GAL3−/− animals compared to WT animals. Moreover, GAL3−/− animals exhibited reduced astrogliosis compared to WT animals. Immunohistochemistry revealed that GAL3−/− animals had a larger area marked for the anti-inflammatory marker Arginase-1 and a smaller area marked for the pro-inflammatory marker iNOS compared to WT animals. We conclude that galectin-3 plays a critical role in the inflammatory process following spinal cord injury, and its absence may contribute to reduced lesion progression, decreased astrogliosis, and the promotion of an inflammatory response with a more anti-inflammatory profile.</div></div><div><h3>Significance statement</h3><div>This study highlights galectin-3 as a central mediator of the inflammatory response after spinal cord injury, demonstrating that galectin-3 deficiency limits lesion progression, attenuates astrogliosis, and promotes an anti-inflammatory profile. Thus, galectin-3 may represent a promising potential therapeutic target for clinical applications in neurodegenerative diseases.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"410 ","pages":"Article 578818"},"PeriodicalIF":2.5,"publicationDate":"2025-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145587881","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

IL-17 and IL-22 in Guillain-Barré syndrome: Untangling disease-specific signals from confounding factors guillain - barr<s:1>综合征中的IL-17和IL-22：从混杂因素中解开疾病特异性信号

IF 2.5 4区医学 Q3 IMMUNOLOGY

Journal of neuroimmunology

Pub Date : 2025-11-21 DOI: 10.1016/j.jneuroim.2025.578820

Christian Messina

引用次数: 0

Neurological adverse events of immune checkpoint inhibitors: A practical guide to diagnosis with a focus on neuroimaging findings 免疫检查点抑制剂的神经系统不良事件：一个实用的诊断指南，重点是神经影像学的发现

IF 2.5 4区医学 Q3 IMMUNOLOGY

Journal of neuroimmunology

Pub Date : 2025-11-21 DOI: 10.1016/j.jneuroim.2025.578816

Simone Rossi , Alberto Vogrig , Laura Fionda , Valentina Damato , Luca Spinardi , Maria Guarino

The use of immune checkpoint inhibitors (ICIs), a class of oncologic therapies that enhance anti-tumor immunity, may be complicated by the occurrence of neurologic immune-related adverse events (n-irAEs). ICI-induced neurotoxicities predominantly affect the peripheral nervous system, manifesting as myositis, polyradiculoneuropathies and cranial neuropathies and, less frequently, involve the central nervous system, typically as encephalitis or myelitis. The diagnosis of n-irAEs relies on the exclusion of alternative etiologies – such as cancer dissemination, chemotherapy-induced neurotoxicities, and neuroinfections – and the recognition of specific clinical syndromes.

Neuroradiological investigations, particularly magnetic resonance imaging (MRI), play a crucial role in ruling out differential diagnosis, mainly cancer dissemination. Furthermore, MRI can support the clinical suspicious of an immune-mediated process by demonstrating indirect signs of neuroinflammation, including tissue edema and gadolinium enhancement. Nuclear medicine techniques, such as position emission tomography and scintigraphy, may also aid in the assessment of ICI-induced encephalitis and parkinsonism.

Despite the recognized clinical relevance of imaging investigations in the diagnosis of n-irAEs, a detailed characterization of neuroradiological features of ICI-induced neurotoxicities remains limited. In this Review, we provide a comprehensive description of the imaging findings associated with n-irAEs and summarize the diagnostic work-up of these challenging disorders, emphasizing the central role of neuroimaging in their evaluation.

免疫检查点抑制剂（ICIs）是一类增强抗肿瘤免疫的肿瘤疗法，其使用可能会因神经免疫相关不良事件（n-irAEs）的发生而复杂化。ici诱导的神经毒性主要影响周围神经系统，表现为肌炎、多根神经病变和颅神经病变，很少累及中枢神经系统，典型表现为脑炎或脊髓炎。n-irAEs的诊断依赖于排除其他病因，如癌症扩散、化疗引起的神经毒性和神经感染，以及对特定临床综合征的识别。神经放射学检查，特别是磁共振成像（MRI），在排除鉴别诊断（主要是癌症扩散）方面起着至关重要的作用。此外，MRI可以通过显示神经炎症的间接迹象（包括组织水肿和钆增强）来支持免疫介导过程的临床怀疑。核医学技术，如位置发射断层扫描和闪烁成像，也可以帮助评估脑损伤引起的脑炎和帕金森病。尽管公认影像学检查在诊断n-irAEs中的临床相关性，但ici诱导的神经毒性的神经放射学特征的详细表征仍然有限。在这篇综述中，我们提供了与n-irAEs相关的影像学发现的全面描述，并总结了这些具有挑战性的疾病的诊断工作，强调了神经影像学在其评估中的核心作用。

{"title":"Neurological adverse events of immune checkpoint inhibitors: A practical guide to diagnosis with a focus on neuroimaging findings","authors":"Simone Rossi , Alberto Vogrig , Laura Fionda , Valentina Damato , Luca Spinardi , Maria Guarino","doi":"10.1016/j.jneuroim.2025.578816","DOIUrl":"10.1016/j.jneuroim.2025.578816","url":null,"abstract":"<div><div>The use of immune checkpoint inhibitors (ICIs), a class of oncologic therapies that enhance anti-tumor immunity, may be complicated by the occurrence of neurologic immune-related adverse events (n-irAEs). ICI-induced neurotoxicities predominantly affect the peripheral nervous system, manifesting as myositis, polyradiculoneuropathies and cranial neuropathies and, less frequently, involve the central nervous system, typically as encephalitis or myelitis. The diagnosis of n-irAEs relies on the exclusion of alternative etiologies – such as cancer dissemination, chemotherapy-induced neurotoxicities, and neuroinfections – and the recognition of specific clinical syndromes.</div><div>Neuroradiological investigations, particularly magnetic resonance imaging (MRI), play a crucial role in ruling out differential diagnosis, mainly cancer dissemination. Furthermore, MRI can support the clinical suspicious of an immune-mediated process by demonstrating indirect signs of neuroinflammation, including tissue edema and gadolinium enhancement. Nuclear medicine techniques, such as position emission tomography and scintigraphy, may also aid in the assessment of ICI-induced encephalitis and parkinsonism.</div><div>Despite the recognized clinical relevance of imaging investigations in the diagnosis of n-irAEs, a detailed characterization of neuroradiological features of ICI-induced neurotoxicities remains limited. In this Review, we provide a comprehensive description of the imaging findings associated with n-irAEs and summarize the diagnostic work-up of these challenging disorders, emphasizing the central role of neuroimaging in their evaluation.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"410 ","pages":"Article 578816"},"PeriodicalIF":2.5,"publicationDate":"2025-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145615380","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Psychopathology in myasthenia gravis: Results from a multicenter Italian study 重症肌无力的精神病理学：来自意大利多中心研究的结果

IF 2.5 4区医学 Q3 IMMUNOLOGY

Journal of neuroimmunology

Pub Date : 2025-11-20 DOI: 10.1016/j.jneuroim.2025.578807

Claudia Vinciguerra , Giuseppe Montalbano , Valentina Virzì , Nicasio Rini , Christian Messina , Liliana Bevilacqua , Paolo Barone , Maria D’Apolito , Eliana Liberatoscioli , Antonio Di Muzio , Roberto Monastero , Filippo Brighina , Vincenzo Di Stefano

Introduction

Myasthenia gravis (MG) is a chronic autoimmune disorder characterized by neuromuscular impairment. While its motor symptoms are well-documented, its neuropsychological impact remains underexplored. This multicenter retrospective case-control study explores the prevalence of psychopathology in MG patients compared to healthy controls (HCs), analyzing correlations between disease severity and psychiatric disorders.

Methods

We retrospectively analyzed 116 MG patients and 119 HCs from three Italian MG centers. Neuropsychological assessment included the Frontal Assessment Battery (FAB) for executive functions, the Beck Depression Inventory (BDI-II) for depression, the 12-Item Short-Form Health Survey (SF-12) for quality of life, the Insomnia Severity Index (ISI) for sleep disturbances, and the Symptom Checklist-90 Revised (SCL-90-R) for psychological distress. Group differences were assessed using ANOVA. In MG patients, correlations between clinical and neuropsychological measures were explored through Pearson's coefficient, while multivariate logistic regression identified predictors of psychiatric involvement.

Results

MG patients exhibited significantly higher SCL-90 total scores and all subdomains (p ≤ 0.001), more frequent sleep disturbances (p = 0.028), and higher BDI-II scores (p ≤ 0.001) than HCs. Increased steroid dosage correlated with anxiety (r = 0.39, p = 0.04), psychoticism (p = 0.021), and depression (p = 0.015). Regression analysis identified disease severity (OR = 2.14, 95 % CI: 1.30–3.51, p = 0.002) and corticosteroid dosage (OR = 1.78, 95 % CI: 1.12–2.83, p = 0.015) as independent predictors of psychiatric symptoms.

Conclusions

MG patients show a significantly higher psychiatric burden, with disease severity and corticosteroid exposure as key contributors. These findings highlight the need for integrated neuropsychiatric monitoring in MG care.

重症肌无力（MG）是一种以神经肌肉损伤为特征的慢性自身免疫性疾病。虽然其运动症状有充分的记录，但其神经心理影响仍未得到充分探讨。这项多中心回顾性病例对照研究探讨了MG患者与健康对照（hc）相比精神病理学的患病率，分析了疾病严重程度与精神障碍之间的相关性。方法回顾性分析来自意大利三个MG中心的116例MG患者和119例hc。神经心理学评估包括执行功能的正面评估组（FAB）、抑郁症的贝克抑郁量表（BDI-II）、生活质量的12项简短健康调查（SF-12）、睡眠障碍的失眠严重程度指数（ISI）和心理困扰的症状检查表-90修订版（SCL-90-R）。采用方差分析评估组间差异。在MG患者中，通过皮尔逊系数探讨临床和神经心理学测量之间的相关性，而多变量逻辑回归确定了精神疾病累及的预测因子。结果smg组患者SCL-90总分及各子域均高于hc组（p≤0.001），睡眠障碍发生率高于HCs组（p = 0.028）， BDI-II评分高于HCs组（p≤0.001）。类固醇剂量增加与焦虑（r = 0.39, p = 0.04）、精神状态（p = 0.021）和抑郁（p = 0.015）相关。回归分析确定疾病严重程度（OR = 2.14, 95% CI: 1.30-3.51, p = 0.002）和皮质类固醇剂量（OR = 1.78, 95% CI: 1.12-2.83, p = 0.015）是精神症状的独立预测因子。结论smg患者精神负担明显加重，疾病严重程度和皮质类固醇暴露是主要影响因素。这些发现强调了在MG护理中进行综合神经精神监测的必要性。

{"title":"Psychopathology in myasthenia gravis: Results from a multicenter Italian study","authors":"Claudia Vinciguerra , Giuseppe Montalbano , Valentina Virzì , Nicasio Rini , Christian Messina , Liliana Bevilacqua , Paolo Barone , Maria D’Apolito , Eliana Liberatoscioli , Antonio Di Muzio , Roberto Monastero , Filippo Brighina , Vincenzo Di Stefano","doi":"10.1016/j.jneuroim.2025.578807","DOIUrl":"10.1016/j.jneuroim.2025.578807","url":null,"abstract":"<div><h3>Introduction</h3><div>Myasthenia gravis (MG) is a chronic autoimmune disorder characterized by neuromuscular impairment. While its motor symptoms are well-documented, its neuropsychological impact remains underexplored. This multicenter retrospective case-control study explores the prevalence of psychopathology in MG patients compared to healthy controls (HCs), analyzing correlations between disease severity and psychiatric disorders.</div></div><div><h3>Methods</h3><div>We retrospectively analyzed 116 MG patients and 119 HCs from three Italian MG centers. Neuropsychological assessment included the Frontal Assessment Battery (FAB) for executive functions, the Beck Depression Inventory (BDI-II) for depression, the 12-Item Short-Form Health Survey (SF-12) for quality of life, the Insomnia Severity Index (ISI) for sleep disturbances, and the Symptom Checklist-90 Revised (SCL-90-R) for psychological distress. Group differences were assessed using ANOVA. In MG patients, correlations between clinical and neuropsychological measures were explored through Pearson's coefficient, while multivariate logistic regression identified predictors of psychiatric involvement.</div></div><div><h3>Results</h3><div>MG patients exhibited significantly higher SCL-90 total scores and all subdomains (<em>p</em> ≤ 0.001), more frequent sleep disturbances (<em>p</em> = 0.028), and higher BDI-II scores (p ≤ 0.001) than HCs. Increased steroid dosage correlated with anxiety (<em>r</em> = 0.39, <em>p</em> = 0.04), psychoticism (<em>p</em> = 0.021), and depression (<em>p</em> = 0.015). Regression analysis identified disease severity (OR = 2.14, 95 % CI: 1.30–3.51, <em>p</em> = 0.002) and corticosteroid dosage (OR = 1.78, 95 % CI: 1.12–2.83, <em>p</em> = 0.015) as independent predictors of psychiatric symptoms.</div></div><div><h3>Conclusions</h3><div>MG patients show a significantly higher psychiatric burden, with disease severity and corticosteroid exposure as key contributors. These findings highlight the need for integrated neuropsychiatric monitoring in MG care.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"410 ","pages":"Article 578807"},"PeriodicalIF":2.5,"publicationDate":"2025-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145569195","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Early exposure of NOD/ShiLtJ mice to Freund's adjuvant prompts delayed, spontaneous progressive encephalomyelitis NOD/ShiLtJ小鼠早期暴露于弗氏佐剂可引起延迟的自发性进行性脑脊髓炎。

IF 2.5 4区医学 Q3 IMMUNOLOGY

Journal of neuroimmunology

Pub Date : 2025-11-19 DOI: 10.1016/j.jneuroim.2025.578809

Giuseppe Ranieri, Alberto Chiarugi, Daniela Buonvicino

Drugs able to efficiently counteract primary progressive MS (PP-MS) remain an unmet need. The availability of reliable animal models of PP-MS might boost the identification of treatments capable of counteracting disease evolution. Recently, we characterized primary progressive EAE (PP-EAE) in NOD/ShiLtJ mice, showing that it recapitulates several key features of PPMS. However, a fundamental difference between PPMS and PPEAE is that the latter is triggered by loss of tolerance deliberately induced via peripheral expansion of myelin-specific effector T cells (Teff). In the present study, we report that NOD/ShiLtJ mice challenged with complete Freund's adjuvant (CFA) to prevent diabetes onset, developed spontaneous PP-EAE (SPP-EAE). Specifically, we report that the sole CFA challenge induced encephalomyelitis with a similar pattern of that prompted by the complete immunization protocol including CFA, pertussis toxin and MOG₃₅_–₅₅. Mice with SPP-EAE show primary progressive disease evolution, widespread neurodegeneration, and insensitivity to dexamethasone-dependent immunosuppression. Remarkably, however, at variance with the rapid onset of PP-EAE, SPP-EAE manifested after a latency of approximately 4.5 months following CFA injection. This model may represent a valuable experimental tool to study mechanisms underlying spontaneous loss of self-tolerance toward CNS antigens and MS progression, as well as to identify therapies of relevance to treatment of PMS patients.

能够有效对抗原发性进行性多发性硬化症（PP-MS）的药物仍然是一个未满足的需求。可靠的PP-MS动物模型的可用性可能会促进能够对抗疾病进化的治疗方法的识别。最近，我们对NOD/ShiLtJ小鼠的原发性进行性EAE （PP-EAE）进行了表征，表明它概括了PPMS的几个关键特征。然而，PPMS和peae之间的根本区别在于，后者是由髓磷脂特异性效应T细胞（Teff）外周扩张故意诱导的耐受性丧失引发的。在本研究中，我们报道NOD/ShiLtJ小鼠用完全弗氏佐剂（CFA）来预防糖尿病发作，发生自发性PP-EAE （SPP-EAE）。具体来说，我们报道了单独的CFA攻击诱导脑脊髓炎的模式与包括CFA，百日咳毒素和MOG35-55在内的完整免疫方案引起的模式相似。SPP-EAE小鼠表现为原发性进行性疾病演变，广泛的神经退行性变，对地塞米松依赖性免疫抑制不敏感。然而，值得注意的是，与PP-EAE的快速发作不同，SPP-EAE在注射CFA后大约4.5个月后才出现。该模型可能是一种有价值的实验工具，用于研究对CNS抗原自发丧失自我耐受性和MS进展的机制，以及确定与PMS患者治疗相关的治疗方法。

{"title":"Early exposure of NOD/ShiLtJ mice to Freund's adjuvant prompts delayed, spontaneous progressive encephalomyelitis","authors":"Giuseppe Ranieri, Alberto Chiarugi, Daniela Buonvicino","doi":"10.1016/j.jneuroim.2025.578809","DOIUrl":"10.1016/j.jneuroim.2025.578809","url":null,"abstract":"<div><div>Drugs able to efficiently counteract primary progressive MS (PP-MS) remain an unmet need. The availability of reliable animal models of PP-MS might boost the identification of treatments capable of counteracting disease evolution. Recently, we characterized primary progressive EAE (PP-EAE) in NOD/ShiLtJ mice, showing that it recapitulates several key features of PPMS. However, a fundamental difference between PPMS and PPEAE is that the latter is triggered by loss of tolerance deliberately induced <em>via</em> peripheral expansion of myelin-specific effector T cells (Teff). In the present study, we report that NOD/ShiLtJ mice challenged with complete Freund's adjuvant (CFA) to prevent diabetes onset, developed spontaneous PP-EAE (SPP-EAE). Specifically, we report that the sole CFA challenge induced encephalomyelitis with a similar pattern of that prompted by the complete immunization protocol including CFA, pertussis toxin and MOG<sub>35</sub><sub>–</sub><sub>55</sub>. Mice with SPP-EAE show primary progressive disease evolution, widespread neurodegeneration, and insensitivity to dexamethasone-dependent immunosuppression. Remarkably, however, at variance with the rapid onset of PP-EAE, SPP-EAE manifested after a latency of approximately 4.5 months following CFA injection. This model may represent a valuable experimental tool to study mechanisms underlying spontaneous loss of self-tolerance toward CNS antigens and MS progression, as well as to identify therapies of relevance to treatment of PMS patients.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"410 ","pages":"Article 578809"},"PeriodicalIF":2.5,"publicationDate":"2025-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145604693","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Ursolic acid enhances social behavior and modulates Th1, Th17, and T regulatory cell-related transcription factor signaling in the BTBR T+ Itpr3tf/J mouse model of autism 熊果酸增强孤独症小鼠BTBR T+ Itpr3tf/J模型中的社会行为并调节Th1、Th17和T调节细胞相关转录因子信号

IF 2.5 4区医学 Q3 IMMUNOLOGY

Journal of neuroimmunology

Pub Date : 2025-11-19 DOI: 10.1016/j.jneuroim.2025.578810

Thamer H. Albekairi, Abdulaziz S. Albakheet, Talal H. Alosaimi, Saleh A. Bakheet, Ahmed Nadeem, Sabry M. Attia, Mushtaq A. Ansari, Marwa H. Hussein, Mohamed A. Mahmoud, Sheikh F. Ahmad

Autism spectrum disorder (ASD) is a complex neurodevelopmental condition characterized by unusual social interactions, limited speech, and repetitive behaviors or hobbies. The BTBR T⁺ Itpr3^tf/J (BTBR) inbred mice are commonly used as a model for ASD because they display many genetic traits associated with autism. Ursolic acid, a naturally occurring compound found in several plants, has shown promise as a treatment for various inflammatory disorders and related experimental models. This study aimed to explore the potential effects of ursolic acid on self-grooming, marble burying, and social behaviors in BTBR mice. We examined how ursolic acid affects the expression of Th1 (IFN-γ, TNF-α, STAT1, STAT4, and T-bet), Th17 (IL-17, RORγt, and STAT3), and T regulatory (Treg; IL-10, TGF-β1, and Foxp3) markers in CD4⁺ T cells within the spleens of BTBR and C57BL/6 mice. Additionally, we assessed the impact of ursolic acid on brain mRNA levels of IFN-γ, TNF-α, STAT1, STAT4, T-bet, IL-17, RORγ, STAT3, IL-10, TGF-β1, and Foxp3. Treatment with ursolic acid significantly affected behavioral issues in BTBR mice. In these animals, ursolic acid reduced the levels of Th1 and Th17 cells while increasing the levels of Treg cells. Furthermore, it decreased the expression of Th1 and Th17 mRNA and increased the expression of Treg-related mRNA in the brain. Our findings suggest that, due to its anti-inflammatory properties, ursolic acid may be a beneficial treatment for behavioral impairments in BTBR mice.

自闭症谱系障碍（ASD）是一种复杂的神经发育疾病，其特征是不寻常的社会互动，有限的语言，重复的行为或爱好。BTBR T+ Itpr3tf/J （BTBR）近交小鼠通常被用作ASD的模型，因为它们显示出许多与自闭症相关的遗传特征。熊果酸是一种在多种植物中发现的天然化合物，有望用于治疗各种炎症性疾病和相关的实验模型。本研究旨在探讨熊果酸对BTBR小鼠自我梳理、大理石掩埋和社会行为的潜在影响。我们研究了熊果酸如何影响BTBR和C57BL/6小鼠脾脏CD4+ T细胞中Th1 （IFN-γ、TNF-α、STAT1、STAT4和T-bet）、Th17 （IL-17、RORγt和STAT3）和T调节（Treg、IL-10、TGF-β1和Foxp3）标志物的表达。此外，我们还评估了熊果酸对脑内IFN-γ、TNF-α、STAT1、STAT4、T-bet、IL-17、RORγ、STAT3、IL-10、TGF-β1和Foxp3 mRNA水平的影响。熊果酸治疗显著影响BTBR小鼠的行为问题。在这些动物中，熊果酸降低了Th1和Th17细胞的水平，同时增加了Treg细胞的水平。降低Th1和Th17 mRNA的表达，增加treg相关mRNA的表达。我们的研究结果表明，由于熊果酸的抗炎特性，熊果酸可能是治疗BTBR小鼠行为障碍的有益方法。

{"title":"Ursolic acid enhances social behavior and modulates Th1, Th17, and T regulatory cell-related transcription factor signaling in the BTBR T+ Itpr3tf/J mouse model of autism","authors":"Thamer H. Albekairi, Abdulaziz S. Albakheet, Talal H. Alosaimi, Saleh A. Bakheet, Ahmed Nadeem, Sabry M. Attia, Mushtaq A. Ansari, Marwa H. Hussein, Mohamed A. Mahmoud, Sheikh F. Ahmad","doi":"10.1016/j.jneuroim.2025.578810","DOIUrl":"10.1016/j.jneuroim.2025.578810","url":null,"abstract":"<div><div>Autism spectrum disorder (ASD) is a complex neurodevelopmental condition characterized by unusual social interactions, limited speech, and repetitive behaviors or hobbies. The BTBR T<sup>+</sup> Itpr3<sup>tf/</sup>J (BTBR) inbred mice are commonly used as a model for ASD because they display many genetic traits associated with autism. Ursolic acid, a naturally occurring compound found in several plants, has shown promise as a treatment for various inflammatory disorders and related experimental models. This study aimed to explore the potential effects of ursolic acid on self-grooming, marble burying, and social behaviors in BTBR mice. We examined how ursolic acid affects the expression of Th1 (IFN-γ, TNF-α, STAT1, STAT4, and T-bet), Th17 (IL-17, RORγt, and STAT3), and T regulatory (Treg; IL-10, TGF-β1, and Foxp3) markers in CD4<sup>+</sup> T cells within the spleens of BTBR and C57BL/6 mice. Additionally, we assessed the impact of ursolic acid on brain mRNA levels of IFN-γ, TNF-α, STAT1, STAT4, T-bet, IL-17, RORγ, STAT3, IL-10, TGF-β1, and Foxp3. Treatment with ursolic acid significantly affected behavioral issues in BTBR mice. In these animals, ursolic acid reduced the levels of Th1 and Th17 cells while increasing the levels of Treg cells. Furthermore, it decreased the expression of Th1 and Th17 mRNA and increased the expression of Treg-related mRNA in the brain. Our findings suggest that, due to its anti-inflammatory properties, ursolic acid may be a beneficial treatment for behavioral impairments in BTBR mice.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"410 ","pages":"Article 578810"},"PeriodicalIF":2.5,"publicationDate":"2025-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145569194","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Syringic acid suppresses inflammation by upregulation of SOCS3 丁香酸通过上调SOCS3抑制炎症

IF 2.5 4区医学 Q3 IMMUNOLOGY

Journal of neuroimmunology

Pub Date : 2025-11-19 DOI: 10.1016/j.jneuroim.2025.578813

Amina Khatun , Surendra Patra , Susovon Chowdhury , Jayasree Saha , Ritobrata Goswami , Shrabani Pradhan , Kuntal Ghosh , Sudipta Chakrabarti

Suppressor of cytokine signalling 3 (SOCS3), a protein that inhibits inflammatory molecules in microglia. A plant-derived phenolic compound, Syringic acid (SA), selectively increased SOCS3 levels in N-9 mouse microglial cells in a dose- and time-dependent manner. Similar effects were also observed in mouse primary microglia and astrocytes. In Lipopolysaccharide (LPS)-stimulated N-9 cells, SOCS3 expression decreased, but after SA treatment (LPS + SA), both mRNA and protein levels of SOCS3 increased. At the same time, pro-inflammatory mediators such as Tumor Necrosis Factor alpha (TNFα), Interleukin-1 receptor, type I (IL1R1), Interleukin-1 beta (IL1β), and Inducible Nitric Oxide Synthase (iNOS) were suppressed, along with a reduction in intracellular Reactive Oxygen Species generation (ROS) in LPS + SA-treated N-9 cells. Additionally, the expression of phospho-CREB was enhanced in LPS + SA-treated N-9 cells compared to only LPS-stimulated cells. Following the SiRNA knockdown of cAMP response element-binding protein (CREB), the upregulation of SOCS3 by syringic acid was abolished. These results confirm the role of CREB in this process. The findings suggest that SA promotes CREB activation, leading to SOCS3 expression, which may have therapeutic potential in neuroinflammatory disorders.

细胞因子信号传导3的抑制因子（SOCS3），一种抑制小胶质细胞炎症分子的蛋白质。一种植物源性酚类化合物丁香酸（SA）以剂量和时间依赖的方式选择性地增加了N-9小鼠小胶质细胞中SOCS3的水平。在小鼠原代小胶质细胞和星形胶质细胞中也观察到类似的效果。在脂多糖（LPS）刺激的N-9细胞中，SOCS3的表达降低，而在SA （LPS + SA）处理后，SOCS3的mRNA和蛋白水平均升高。同时，促炎介质如肿瘤坏死因子α (TNFα)、白细胞介素-1受体I型（IL1R1）、白细胞介素-1 β (IL1β)和诱导型一氧化氮合酶（iNOS）被抑制，同时LPS + sa处理的N-9细胞内活性氧生成（ROS）减少。此外，与仅LPS刺激的细胞相比，LPS + sa处理的N-9细胞中phospho-CREB的表达增强。在cAMP反应元件结合蛋白（CREB）的SiRNA被敲低后，丁香酸对SOCS3的上调作用被消除。这些结果证实了CREB在这一过程中的作用。研究结果表明，SA促进CREB活化，导致SOCS3表达，可能具有治疗神经炎性疾病的潜力。

{"title":"Syringic acid suppresses inflammation by upregulation of SOCS3","authors":"Amina Khatun , Surendra Patra , Susovon Chowdhury , Jayasree Saha , Ritobrata Goswami , Shrabani Pradhan , Kuntal Ghosh , Sudipta Chakrabarti","doi":"10.1016/j.jneuroim.2025.578813","DOIUrl":"10.1016/j.jneuroim.2025.578813","url":null,"abstract":"<div><div>Suppressor of cytokine signalling 3 (SOCS3), a protein that inhibits inflammatory molecules in microglia. A plant-derived phenolic compound, Syringic acid (SA), selectively increased SOCS3 levels in N-9 mouse microglial cells in a dose- and time-dependent manner. Similar effects were also observed in mouse primary microglia and astrocytes. In Lipopolysaccharide (LPS)-stimulated N-9 cells, SOCS3 expression decreased, but after SA treatment (LPS + SA), both mRNA and protein levels of SOCS3 increased. At the same time, pro-inflammatory mediators such as Tumor Necrosis Factor alpha (TNFα), Interleukin-1 receptor, type I (IL1R1), Interleukin-1 beta (IL1β), and Inducible Nitric Oxide Synthase (iNOS) were suppressed, along with a reduction in intracellular Reactive Oxygen Species generation (ROS) in LPS + SA-treated N-9 cells. Additionally, the expression of phospho-CREB was enhanced in LPS + SA-treated N-9 cells compared to only LPS-stimulated cells. Following the SiRNA knockdown of cAMP response element-binding protein (CREB), the upregulation of SOCS3 by syringic acid was abolished. These results confirm the role of CREB in this process. The findings suggest that SA promotes CREB activation, leading to SOCS3 expression, which may have therapeutic potential in neuroinflammatory disorders.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"410 ","pages":"Article 578813"},"PeriodicalIF":2.5,"publicationDate":"2025-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145569186","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Characteristics and prognosis of PCA-1 (anti-Yo) autoimmunity and the utility of the Brief Ataxia Rating Scale in a seropositive cerebellar ataxia cohort PCA-1（抗- yo）自身免疫的特点和预后以及简要共济失调评定量表在血清阳性小脑性共济失调队列中的应用

IF 2.5 4区医学 Q3 IMMUNOLOGY

Journal of neuroimmunology

Pub Date : 2025-11-19 DOI: 10.1016/j.jneuroim.2025.578812

Sophia Cerroni , Yoji Hoshina , Trevor Glenn , Nupur Goel , Bruna Leles Vieira de Souza , Joao Vitor Mahler , Mattia Wruble , Giovanna S. Manzano

Background

Autoimmune cerebellar ataxia (ACA), whether paraneoplastic, classically associated with PCA-1 autoimmunity, or non-paraneoplastic, causes substantial morbidity. Antibodies inform clinical decisions given prognostic differences. The modified Rankin Scale (mRS) and Clinical Assessment Scale in Autoimmune Encephalitis (CASE) underrepresent cerebellar change. We aimed to characterize seropositive ACA, compare PCA-1 with other seropositive cases, identify predictors of poor function, and compare outcome measures.

Methods

We performed a retrospective cohort study of adults with seropositive ACA at Massachusetts General Brigham (2004–2025). We compared anti-PCA-1 positive with other seropositive cohorts. Time to wheelchair dependence was estimated by Kaplan-Meier and compared by log-rank. Univariable Cox models identified predictors. Outcomes were assessed with mRS, CASE, and Brief Ataxia Rating Scale (BARS).

Results

Nineteen patients (median age 66.3 years; 68.4 % female) were included. Eleven (57.9 %) were anti-PCA-1 positive and all of them were paraneoplastic. Tubo-ovarian serous carcinoma was most common (63.6 %). The anti-PCA-1 positive group was more often female (90.9 % vs. 37.5 % p = 0.04), had worse BARS at last follow up (20 vs. 9.5 p < 0.01), and had higher wheelchair dependence (100 % vs. 37.5 % p < 0.01). Acute onset (< 2 weeks) and PCA-1 positivity were associated with wheelchair dependence. BARS monitored symptoms more precisely than mRS or CASE.

Conclusion

In this seropositive ACA cohort, PCA-1 autoimmunity was associated with wheelchair dependence despite immunotherapy and cancer treatment. Acute onset may predict severe decline. A cerebellar symptom specific measure such as BARS may assess clinical change better than mRS or CASE for monitoring ACA.

自身免疫性小脑性共济失调（ACA），无论是与典型的PCA-1自身免疫相关的副肿瘤性，还是非副肿瘤性，都会导致大量的发病率。鉴于预后差异，抗体可为临床决策提供信息。改进的Rankin量表（mRS）和自身免疫性脑炎临床评估量表（CASE）不能充分反映小脑的变化。我们的目的是表征血清ACA阳性，比较PCA-1与其他血清阳性病例，确定功能不良的预测因素，并比较结果测量。方法：我们对2004-2025年在马萨诸塞州布里格姆总医院（Massachusetts General Brigham）的成人血清ACA阳性患者进行了回顾性队列研究。我们比较了抗pca -1阳性与其他血清阳性的队列。到轮椅依赖的时间用Kaplan-Meier法估计，用log-rank法比较。单变量Cox模型确定了预测因子。结果用mRS、CASE和简短共济失调评定量表（BARS）进行评估。结果共纳入19例患者，中位年龄66.3岁，女性68.4%。抗pca -1阳性11例（57.9%），均为副肿瘤。输卵管卵巢浆液性癌最常见（63.6%）。抗pca -1阳性组多为女性（90.9%比37.5% p = 0.04），最后随访时BARS较差（20比9.5 p < 0.01），轮椅依赖性较高（100%比37.5% p < 0.01）。急性发作（2周）和PCA-1阳性与轮椅依赖有关。BARS比mRS或CASE更精确地监测症状。结论在这个血清ACA阳性的队列中，尽管免疫治疗和癌症治疗，PCA-1自身免疫与轮椅依赖相关。急性发作可预示严重衰退。在监测ACA方面，小脑症状特异性测量（如BARS）可能比mRS或CASE更好地评估临床变化。

{"title":"Characteristics and prognosis of PCA-1 (anti-Yo) autoimmunity and the utility of the Brief Ataxia Rating Scale in a seropositive cerebellar ataxia cohort","authors":"Sophia Cerroni , Yoji Hoshina , Trevor Glenn , Nupur Goel , Bruna Leles Vieira de Souza , Joao Vitor Mahler , Mattia Wruble , Giovanna S. Manzano","doi":"10.1016/j.jneuroim.2025.578812","DOIUrl":"10.1016/j.jneuroim.2025.578812","url":null,"abstract":"<div><h3>Background</h3><div>Autoimmune cerebellar ataxia (ACA), whether paraneoplastic, classically associated with PCA-1 autoimmunity, or non-paraneoplastic, causes substantial morbidity. Antibodies inform clinical decisions given prognostic differences. The modified Rankin Scale (mRS) and Clinical Assessment Scale in Autoimmune Encephalitis (CASE) underrepresent cerebellar change. We aimed to characterize seropositive ACA, compare PCA-1 with other seropositive cases, identify predictors of poor function, and compare outcome measures.</div></div><div><h3>Methods</h3><div>We performed a retrospective cohort study of adults with seropositive ACA at Massachusetts General Brigham (2004–2025). We compared anti-PCA-1 positive with other seropositive cohorts. Time to wheelchair dependence was estimated by Kaplan-Meier and compared by log-rank. Univariable Cox models identified predictors. Outcomes were assessed with mRS, CASE, and Brief Ataxia Rating Scale (BARS).</div></div><div><h3>Results</h3><div>Nineteen patients (median age 66.3 years; 68.4 % female) were included. Eleven (57.9 %) were anti-PCA-1 positive and all of them were paraneoplastic. Tubo-ovarian serous carcinoma was most common (63.6 %). The anti-PCA-1 positive group was more often female (90.9 % vs. 37.5 % <em>p</em> = 0.04), had worse BARS at last follow up (20 vs. 9.5 <em>p</em> < 0.01), and had higher wheelchair dependence (100 % vs. 37.5 % p < 0.01). Acute onset (< 2 weeks) and PCA-1 positivity were associated with wheelchair dependence. BARS monitored symptoms more precisely than mRS or CASE.</div></div><div><h3>Conclusion</h3><div>In this seropositive ACA cohort, PCA-1 autoimmunity was associated with wheelchair dependence despite immunotherapy and cancer treatment. Acute onset may predict severe decline. A cerebellar symptom specific measure such as BARS may assess clinical change better than mRS or CASE for monitoring ACA.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"410 ","pages":"Article 578812"},"PeriodicalIF":2.5,"publicationDate":"2025-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145569196","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Identification of the core genes KLRB1 and RETN as potential shared diagnostic markers for major depressive disorder and systemic lupus erythematosus through bioinformatics and machine learning methodologies 通过生物信息学和机器学习方法鉴定核心基因KLRB1和RETN作为重性抑郁症和系统性红斑狼疮的潜在共同诊断标志物

IF 2.5 4区医学 Q3 IMMUNOLOGY

Journal of neuroimmunology

Pub Date : 2025-11-19 DOI: 10.1016/j.jneuroim.2025.578811

Ruoling Jia, Xubin Yao, Qingling Liu, Xun Wang

This study investigates the shared molecular mechanisms between major depressive disorder (MDD) and systemic lupus erythematosus (SLE) through integrated bioinformatics analysis. Analysis of multiple GEO datasets identified 23 common differentially expressed genes (coDEGs), primarily enriched in immune and metabolic pathways. Among 13 high-confidence hub genes derived from protein-protein interaction networks, two biomarkers—KLRB1 and RETN—were consistently selected by machine learning algorithms (including LASSO, SVM, and Random Forest) and validated across independent cohorts. Both biomarkers demonstrated high diagnostic accuracy, with combined AUC values of 0.929 for MDD and 0.948 for SLE. Immune infiltration analysis revealed common reductions in NK cells and elevated monocyte levels in both disorders. KLRB1 expression was positively correlated with NK cell function, while RETN showed disease-specific immune correlations. Gene Set Enrichment Analysis (GSEA) indicated associations between both genes and neurodegeneration-related pathways. Additionally, a predicted ceRNA network suggested potential upstream non-coding RNA regulators. These results underscore dysregulated innate immunity and inflammatory pathways as key common features of MDD and SLE, providing new insights into their diagnosis and therapeutic targeting.

本研究通过综合生物信息学分析探讨了重度抑郁症（MDD）和系统性红斑狼疮（SLE）之间的共同分子机制。对多个GEO数据集的分析鉴定出23个共同差异表达基因（coDEGs），主要富集于免疫和代谢途径。在来自蛋白质相互作用网络的13个高置信度中心基因中，通过机器学习算法（包括LASSO、SVM和Random Forest）一致地选择了两个生物标志物——klrb1和retn，并在独立的队列中进行了验证。两种生物标志物均显示出较高的诊断准确性，MDD的综合AUC值为0.929，SLE的综合AUC值为0.948。免疫浸润分析显示，在这两种疾病中，NK细胞普遍减少，单核细胞水平升高。KLRB1表达与NK细胞功能呈正相关，RETN表达与疾病特异性免疫相关。基因集富集分析（GSEA）表明这两个基因与神经变性相关途径之间存在关联。此外，预测的ceRNA网络提示了潜在的上游非编码RNA调节因子。这些结果强调先天免疫和炎症通路失调是MDD和SLE的关键共同特征，为其诊断和治疗靶向提供了新的见解。

{"title":"Identification of the core genes KLRB1 and RETN as potential shared diagnostic markers for major depressive disorder and systemic lupus erythematosus through bioinformatics and machine learning methodologies","authors":"Ruoling Jia, Xubin Yao, Qingling Liu, Xun Wang","doi":"10.1016/j.jneuroim.2025.578811","DOIUrl":"10.1016/j.jneuroim.2025.578811","url":null,"abstract":"<div><div>This study investigates the shared molecular mechanisms between major depressive disorder (MDD) and systemic lupus erythematosus (SLE) through integrated bioinformatics analysis. Analysis of multiple GEO datasets identified 23 common differentially expressed genes (coDEGs), primarily enriched in immune and metabolic pathways. Among 13 high-confidence hub genes derived from protein-protein interaction networks, two biomarkers—KLRB1 and RETN—were consistently selected by machine learning algorithms (including LASSO, SVM, and Random Forest) and validated across independent cohorts. Both biomarkers demonstrated high diagnostic accuracy, with combined AUC values of 0.929 for MDD and 0.948 for SLE. Immune infiltration analysis revealed common reductions in NK cells and elevated monocyte levels in both disorders. KLRB1 expression was positively correlated with NK cell function, while RETN showed disease-specific immune correlations. Gene Set Enrichment Analysis (GSEA) indicated associations between both genes and neurodegeneration-related pathways. Additionally, a predicted ceRNA network suggested potential upstream non-coding RNA regulators. These results underscore dysregulated innate immunity and inflammatory pathways as key common features of MDD and SLE, providing new insights into their diagnosis and therapeutic targeting.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"410 ","pages":"Article 578811"},"PeriodicalIF":2.5,"publicationDate":"2025-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145569185","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Prior dexamethasone exposure attenuates the therapeutic efficacy of mouse bone marrow-derived mesenchymal stem cells in experimental autoimmune encephalomyelitis by fostering a hostile immunological microenvironment 先前暴露于地塞米松通过培养敌对免疫微环境减弱小鼠骨髓源间充质干细胞治疗实验性自身免疫性脑脊髓炎的疗效。

IF 2.5 4区医学 Q3 IMMUNOLOGY

Journal of neuroimmunology

Pub Date : 2025-11-19 DOI: 10.1016/j.jneuroim.2025.578814

Yaling Zhang , Xiaoqiang Lv , Qing Wang , Xuan Ma , Ruotong Wu , Tingting Cui , Xiaoli Ding , Qian Zhang , Luting Yang , Cungen Ma , Yaping Yan

Bone marrow-derived mesenchymal stem cells (BMSCs) are promising candidates for treating autoimmune diseases like multiple sclerosis (MS) due to their ability to differentiate into multiple lineages and their immunomodulatory properties. However, the immunomodulatory capacity of BMSCs is highly adaptable, and primarily regulated by inflammatory factors. In this study, we evaluated the therapeutic effectiveness of BMSCs in dexamethasone (DEX)-pretreated experimental autoimmune encephalomyelitis (EAE) mice. Our results demonstrated a significant interaction between DEX and BMSCs. In contrast to their effect in non-pretreated mice, BMSCs administration in DEX-pretreated EAE mice resulted in a significant increase in infiltrating CD4⁺ T cells and a concomitant decrease in regulatory T (Treg) cell populations in the central nerves system, which likely resulted from DEX-induced changes in the peripheral immune microenvironment. Our findings in the EAE model indicate that the immune microenvironment established by DEX pretreatment is detrimental to the efficacy of BMSC therapy. This preclinical evidence suggests that evaluating the peripheral immune status may be a critical consideration for future clinical studies of MSC treatment in MS.

骨髓间充质干细胞（BMSCs）由于其分化为多个谱系的能力和其免疫调节特性，是治疗多发性硬化症（MS）等自身免疫性疾病的有希望的候选者。然而，骨髓间充质干细胞的免疫调节能力是高度适应性的，主要受炎症因子调节。在这项研究中，我们评估了骨髓间充质干细胞对地塞米松（DEX）预处理的实验性自身免疫性脑脊髓炎（EAE）小鼠的治疗效果。我们的研究结果表明，DEX和骨髓间充质干细胞之间存在显著的相互作用。与未预处理小鼠相比，经dex预处理的EAE小鼠给药BMSCs导致浸润CD4+ T细胞显著增加，同时中枢神经系统中调节性T （Treg）细胞群减少，这可能是由于dex诱导的外周免疫微环境的变化。我们在EAE模型中的研究结果表明，DEX预处理建立的免疫微环境不利于BMSC治疗的疗效。这一临床前证据表明，评估外周免疫状态可能是未来MSC治疗MS临床研究的关键考虑因素。

{"title":"Prior dexamethasone exposure attenuates the therapeutic efficacy of mouse bone marrow-derived mesenchymal stem cells in experimental autoimmune encephalomyelitis by fostering a hostile immunological microenvironment","authors":"Yaling Zhang , Xiaoqiang Lv , Qing Wang , Xuan Ma , Ruotong Wu , Tingting Cui , Xiaoli Ding , Qian Zhang , Luting Yang , Cungen Ma , Yaping Yan","doi":"10.1016/j.jneuroim.2025.578814","DOIUrl":"10.1016/j.jneuroim.2025.578814","url":null,"abstract":"<div><div>Bone marrow-derived mesenchymal stem cells (BMSCs) are promising candidates for treating autoimmune diseases like multiple sclerosis (MS) due to their ability to differentiate into multiple lineages and their immunomodulatory properties. However, the immunomodulatory capacity of BMSCs is highly adaptable, and primarily regulated by inflammatory factors. In this study, we evaluated the therapeutic effectiveness of BMSCs in dexamethasone (DEX)-pretreated experimental autoimmune encephalomyelitis (EAE) mice. Our results demonstrated a significant interaction between DEX and BMSCs. In contrast to their effect in non-pretreated mice, BMSCs administration in DEX-pretreated EAE mice resulted in a significant increase in infiltrating CD4<sup>+</sup> T cells and a concomitant decrease in regulatory T (Treg) cell populations in the central nerves system, which likely resulted from DEX-induced changes in the peripheral immune microenvironment. Our findings in the EAE model indicate that the immune microenvironment established by DEX pretreatment is detrimental to the efficacy of BMSC therapy. This preclinical evidence suggests that evaluating the peripheral immune status may be a critical consideration for future clinical studies of MSC treatment in MS.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"410 ","pages":"Article 578814"},"PeriodicalIF":2.5,"publicationDate":"2025-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145604673","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0