Journal of neuroimmunology最新文献_第3页

IgLON5 autoimmunity secondary to immune checkpoint inhibitor 免疫检查点抑制剂继发的IgLON5自身免疫。

IF 2.9 4区医学

Journal of neuroimmunology Pub Date : 2024-12-16 DOI: 10.1016/j.jneuroim.2024.578516

Christopher Itoh , Grace Swart , Erik St. Louis , Manish Gandhi , Divyanshu Dubey

引用次数: 0

Guhong injection attenuates brain injury and promotes neuroprotection after acute ischemic stroke 骨红注射液可减轻急性缺血性脑卒中后脑损伤，促进神经保护。

IF 2.9 4区医学

Journal of neuroimmunology Pub Date : 2024-12-15 DOI: 10.1016/j.jneuroim.2024.578515

Xiaoshan Du , Zhihui Qi , Yulin Li, Siting Wu, Fang Zhang, Zhiguo Li, Jingshan Chen

{"title":"Guhong injection attenuates brain injury and promotes neuroprotection after acute ischemic stroke","authors":"Xiaoshan Du , Zhihui Qi , Yulin Li, Siting Wu, Fang Zhang, Zhiguo Li, Jingshan Chen","doi":"10.1016/j.jneuroim.2024.578515","DOIUrl":"10.1016/j.jneuroim.2024.578515","url":null,"abstract":"<div><h3>Background and objectives</h3><div>Guhong injection (GHI) has multiple components and generates diverse effects, and is mainly used in the treatment of acute ischemic stroke (AIS). The purpose of this study is to explore the multiple effects of GHI in AIS models in mice and the mechanism how they work together to affect the stroke outcome.</div></div><div><h3>Methods</h3><div>Middle cerebral artery occlusion (MCAO) and photothrombotic stroke models were established with GHI or vehicle. Neurological function assessment including the Modified Neurological Severity Score (mNSS) and rota-rod test, and relative cerebral blood flow were monitored at day 1 and day 3 after model establishment. Flow cytometry, 2, 3, 5-Triphenyltetrazolium chloride (TTC) staining, histology and immunofluorescence, Western blotting (WB) assay were performed at day 3.</div></div><div><h3>Results</h3><div>The mean mNSS score was lower and the latency to falling off the rota-rod was prolonged at day 3 in the GHI group. GHI reduced the relative infarct volume and increased the relative cerebral blood flow. The histopathological damage of ischemic core was significantly ameliorated in the GHI group. GHI decreased the Caspase-3<sup>+</sup> cells and increased the MAP-2<sup>+</sup> and Claudin-5<sup>+</sup> cells. GHI increased the expression of Bcl-2 and the ratio of Bcl-2/Bax, and decreased the expression levels of Bax, Caspase-3 and Cleaved-Caspased-3. GHI reduced the microglia, decreased the IL-6 positive cells, TNF-α positive cells and increased TGF-β1 positive cells.</div></div><div><h3>Conclusions</h3><div>GHI alleviated brain injury and neurological deficits through improving cerebral blood circulation, attenuating neuronal apoptosis, reducing the disruption of blood-brain barrier (BBB) and decreasing neuroinflammation in MCAO and photothrombotic stroke models in mice. GHI has certain neuroprotective function to be applied to clinical use.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"399 ","pages":"Article 578515"},"PeriodicalIF":2.9,"publicationDate":"2024-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142854620","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

Exploring the immunomodulatory effects of sertraline: Cytokine modulation and signaling pathway dynamics 探索舍曲林的免疫调节作用：细胞因子调节和信号通路动力学。

IF 2.9 4区医学

Journal of neuroimmunology Pub Date : 2024-12-14 DOI: 10.1016/j.jneuroim.2024.578514

Harika Topal Önal , Derya Yetkin , Furkan Ayaz

{"title":"Exploring the immunomodulatory effects of sertraline: Cytokine modulation and signaling pathway dynamics","authors":"Harika Topal Önal , Derya Yetkin , Furkan Ayaz","doi":"10.1016/j.jneuroim.2024.578514","DOIUrl":"10.1016/j.jneuroim.2024.578514","url":null,"abstract":"<div><div>This study explores the nuanced immunomodulatory effects of sertraline, which is widely used in the treatment of major depression, obsessive-compulsive disorder, and anxiety in adults and children. Recent investigations have emphasized the intricate interplay between depression and the body's inflammatory response. This has sparked an exploration into the impact of sertraline on the immune system, an area that still awaits comprehensive exploration.</div><div>Our research methodically examines the influence of sertraline on the levels of cytokines (TNF-a, IL-6, IL-12p40, GM-CSF) in the macrophage cell line J774.2. This analysis is conducted under conditions with and without the lipopolysaccharide (LPS) danger signal. To enhance specificity, sertraline's effects are juxtaposed with those of salicylic acid, a known anti-inflammatory agent. Furthermore, a comprehensive exploration of sertraline's impact on the intracellular signaling pathways regulated phosphoinositide-3-kinase (PI3K) and the p38 pathway is the third major signaling cassettes of the mitogen-activated protein kinase (MAPK) signaling is presented.</div><div>The outcomes of our study unveil distinctive patterns in sertraline's modulation of cytokine levels within macrophage cells. Under the influence of the LPS danger signal, sertraline exhibits immunostimulatory characteristics, contrasting with its ability to suppress GM-CSF cytokine levels, even in the presence of LPS. Notably, the p38 pathway portrays a pro-inflammatory role for sertraline, while inhibiting the PI3K signaling pathway highlights its anti-inflammatory attributes. These findings contribute novel insights into the intricate interplay between sertraline and the immune system.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"399 ","pages":"Article 578514"},"PeriodicalIF":2.9,"publicationDate":"2024-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142872379","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

Therapeutic development towards T follicular helper cells as a molecular target in myasthenia gravis disease T滤泡辅助细胞作为重症肌无力疾病分子靶点的治疗进展。

IF 2.9 4区医学

Journal of neuroimmunology Pub Date : 2024-12-05 DOI: 10.1016/j.jneuroim.2024.578503

J.J. Hernández Ruiz, A.M.C. Romero Malacara, L.A. López Mota, M.J. Pérez Guzmán

引用次数: 0

Quantitative assessment of thalamic damage and serum neurofilament light chain in relapsing-remitting multiple sclerosis 复发-缓解型多发性硬化症丘脑损伤及血清神经丝轻链定量评价。

IF 2.9 4区医学

Journal of neuroimmunology Pub Date : 2024-12-04 DOI: 10.1016/j.jneuroim.2024.578504

Yan Liang , Jing Huang , Xiyue Zhang , Fang Xu , Chunrui Bo , Ming Lin , Xinmei Wen

{"title":"Quantitative assessment of thalamic damage and serum neurofilament light chain in relapsing-remitting multiple sclerosis","authors":"Yan Liang , Jing Huang , Xiyue Zhang , Fang Xu , Chunrui Bo , Ming Lin , Xinmei Wen","doi":"10.1016/j.jneuroim.2024.578504","DOIUrl":"10.1016/j.jneuroim.2024.578504","url":null,"abstract":"<div><h3>Background</h3><div>The study assessed group differences in the thalamus microstructural parameters among healthy individuals and relapsing-remitting multiple sclerosis (RRMS) patients and examined the relationship between quantitative MRI (qMRI) parameters and neurological scores, T2 lesion load, and serum neurofilament light chain (sNfL) levels.</div></div><div><h3>Methods</h3><div>A total of 30 patients with RRMS and 26 age- and sex-matched healthy controls were recruited in this study. The qMRI images were obtained from these individuals. T2 lesion load, thalamic volume, and parameters of thalamic subnuclei were estimated. The neurological functions of participants were assessed using a battery of tests. sNfL concentrations were measured using the single molecule array (SIMOA) technique.</div></div><div><h3>Results</h3><div>T2 relaxometry in the whole thalamus and its subnuclei were increased, and showed an apparent correlation with T2 lesion load and the severity of MS (EDSS, MSSS, 9HPT, T25FW, SDMT). T1 variability was prolonged in most thalamic subnuclei, and it was correlated with the severity of MS (EDSS, 9HPT, SDMT). Thalamic volumetric parameters of MS patients were smaller than those of healthy controls (<em>p</em> < 0.001) and showed an apparent correlation with MS severity. Surprisingly, sNfL levels showed no correlation with T2 relaxometry, T1 variability, or thalamic volumetric parameters.</div></div><div><h3>Conclusion</h3><div>Quantitative synthetic MRI, especially, the metric T2 relaxation times provides a surrogate parameter for assessing underlying thalamic and subnuclei damage in the RRMS group. Integrating structural and quantitative MRI allows a better assessment of the neurodegeneration in the normal-appearing thalamus of RRMS.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"399 ","pages":"Article 578504"},"PeriodicalIF":2.9,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142794848","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A complex and severe encephalitis associated with four co-existing neuronal cell-surface autoantibodies 一种复杂而严重的脑炎，与四种共存的神经元细胞表面自身抗体有关。

IF 2.9 4区医学

Journal of neuroimmunology Pub Date : 2024-12-03 DOI: 10.1016/j.jneuroim.2024.578501

Michael Gilligan , Luke O’Donnell , Andrew Westbrook , Niall Tubridy , Sean O'Riordan , Christopher McGuigan , Sean Connolly , Michael Farrell , Patrick Waters , Sarosh R. Irani , Justin A. Kinsella

{"title":"A complex and severe encephalitis associated with four co-existing neuronal cell-surface autoantibodies","authors":"Michael Gilligan , Luke O’Donnell , Andrew Westbrook , Niall Tubridy , Sean O'Riordan , Christopher McGuigan , Sean Connolly , Michael Farrell , Patrick Waters , Sarosh R. Irani , Justin A. Kinsella","doi":"10.1016/j.jneuroim.2024.578501","DOIUrl":"10.1016/j.jneuroim.2024.578501","url":null,"abstract":"<div><div>Many forms of autoimmune encephalitis are mediated by neuronal cell-surface directed autoantibodies. The co-occurrence of four neuronal cell-surface antibodies in a single patient is exceptionally rare. We report a patient who had a severe encephalitis associated with antibodies to NMDA, Glycine, GABA<sub>A</sub> and GABA<sub>B</sub> receptors. Case: A 28-year-old man on tacrolimus presented with a first seizure. Thereafter, he developed confusion, cerebellar signs, opsoclonus, neuromyotonia and medication-refractory seizures. CSF sampling revealed 826 white cells and NMDA, glycine and GABA<sub>B</sub> receptor antibodies: all were also detected in serum along with additional GABA<sub>A</sub> receptor antibodies. Neural antibodies were detected using fixed (NMDA, GABA<sub>A</sub>, GABA<sub>B</sub> receptor) or live (glycine receptor) cell-based assays at Oxford Neuroimmunology Laboratory, Oxford, UK. MRI brain demonstrated cerebellar leptomeningeal enhancement and a hyperintense lesion in the cerebellar vermis. EEG revealed extreme delta brush and needle EMG confirmed neuromyotonia. No underlying malignancy was detected. Methylprednisolone, IVIG, Rituximab, therapeutic plasma exchange, cyclophosphamide and bortezomib were administered sequentially, with minimal clinical improvement. Death secondary to respiratory sepsis occurred on the 714th hospital day. Postmortem revealed pan-cerebellar atrophy with Purkinje cell loss; dentate nucleus ganglionopathy, and thoracolumbar cord myelopathy. In summary, the detection of multiple neuronal cell-surface antibodies in autoimmune encephalitis is unusual and may result in a complex overlap syndrome with a poor response to immunotherapy.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"399 ","pages":"Article 578501"},"PeriodicalIF":2.9,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142794847","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

Elevated frequencies of activated memory B cells in multiple sclerosis are reset to healthy control levels after B cell depletion with Ocrelizumab 在使用Ocrelizumab消耗B细胞后，多发性硬化症患者激活记忆B细胞的频率升高被重置为健康控制水平。

IF 2.9 4区医学

Journal of neuroimmunology Pub Date : 2024-12-02 DOI: 10.1016/j.jneuroim.2024.578502

Cody J. Gurski , Zivar Hajiyeva , Anthony J. Veltri , Kaylan Fenton , Samantha O'Dell , Ahmed Z. Obeidat , Bonnie N. Dittel

{"title":"Elevated frequencies of activated memory B cells in multiple sclerosis are reset to healthy control levels after B cell depletion with Ocrelizumab","authors":"Cody J. Gurski , Zivar Hajiyeva , Anthony J. Veltri , Kaylan Fenton , Samantha O'Dell , Ahmed Z. Obeidat , Bonnie N. Dittel","doi":"10.1016/j.jneuroim.2024.578502","DOIUrl":"10.1016/j.jneuroim.2024.578502","url":null,"abstract":"<div><div>In multiple sclerosis (MS) the B cell depleting drug ocrelizumab has shown high efficacy in reducing inflammatory activity. Its mechanism of action is unclear due to B cell subset complexity and unknown roles in pathogenesis. Here, we comprehensively phenotyped and quantitated peripheral blood B cell subsets before and after ocrelizumab infusion to gain insight into the fate of B cell subsets with pathogenic potential. Peripheral blood B cells were collected from treatment naïve patients at baseline and months one, three, and six following the first course of ocrelizumab treatment; at 6 months following the second treatment cycle; ∼14 months following their last infusion; and from healthy controls. Flow cytometry combined with cluster analysis was used to track depletion and repletion of naïve, memory, and antibody secreting cells. By month one, naïve B cells were depleted, but a small subset of memory B cells were retained with no depletion of antibody secreting cells. Uniform manifold approximation and projection for dimension reduction analysis of flow cytometry data revealed two non-class switched naïve clusters and two class switched memory clusters. One class switched cluster was activated in MS patients but largely absent in healthy controls. Both memory B cell subsets underwent depletion after a single six-month course of ocrelizumab treatment after which their proportions were reset to heathy control levels. These observations suggest that activated class-switched memory B cells could serve as a biomarker of recent or ongoing MS disease activity to guide redosing.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"399 ","pages":"Article 578502"},"PeriodicalIF":2.9,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142791954","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Chronic g-CSF increases the neutrophil-lymphocyte ratio and decreases plasma corticosterone concentrations in Peromyscus maniculatus without impacting compulsive-like stereotypy 慢性 g-CSF 可提高中性粒细胞-淋巴细胞比率，降低啮齿类动物血浆皮质酮浓度，但不会影响强迫性刻板行为

IF 2.9 4区医学

Journal of neuroimmunology Pub Date : 2024-11-25 DOI: 10.1016/j.jneuroim.2024.578490

J.P. Strydom, Linda Brand, Francois P. Viljoen, De Wet Wolmarans

{"title":"Chronic g-CSF increases the neutrophil-lymphocyte ratio and decreases plasma corticosterone concentrations in Peromyscus maniculatus without impacting compulsive-like stereotypy","authors":"J.P. Strydom, Linda Brand, Francois P. Viljoen, De Wet Wolmarans","doi":"10.1016/j.jneuroim.2024.578490","DOIUrl":"10.1016/j.jneuroim.2024.578490","url":null,"abstract":"<div><div>Increasing evidence points to brain-immune mechanisms underlying conditions characterized by neurocognitive rigidity. However, causal evidence remains elusive. Thus, the present work first aimed to investigate the naturalistic associations between rigid motor stereotypy and non-specific markers of systemic inflammation, i.e., the neutrophil-lymphocyte ratio (NLR) and plasma corticosterone concentrations in deer mice. We then explored causal immune-brain interactions by bolstering the NLR, using the recombinant human granulocyte colony-stimulating factor (g-CSF), i.e., pegfilgrastim (Peg). One-hundred and twenty (120) 3-week-old deer mice (both sexes) were exposed to nine weekly injections with normal water for injection or Peg (<em>n</em> = 60 per group) and then assessed for stereotypical expression. Stereotypical behaviour, the NLR, and plasma corticosterone were then measured. Our findings show that 1) NLR and plasma corticosterone concentrations do not predict stereotypical expression and 2) chronic Peg exposure significantly increased the NLR and decreased the plasma corticosterone concentration in mice of both sexes, without impacting stereotypical expression. While valuable findings related to the relationship between exogenous NLR manipulation and immune system functioning were highlighted, continued investigation will be necessary to further explore whether spontaneous stereotypy in deer mice may be associated with immune-inflammatory involvement.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"398 ","pages":"Article 578490"},"PeriodicalIF":2.9,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142720262","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The role of the immune system in Parkinson's disease pathogenesis: A focus on Th17 cells - A systematic review and meta-analysis 免疫系统在帕金森病发病机制中的作用：聚焦Th17细胞--系统综述与荟萃分析。

IF 2.9 4区医学

Journal of neuroimmunology Pub Date : 2024-11-17 DOI: 10.1016/j.jneuroim.2024.578484

Zihan Jiang , Honghao Huang , Yiqun Chen , Haobo Xie , Yangguang Lu , Yaoyin Ge , Ruotong Yao , Lingsheng Wang , Zihao Wu , Yiran Bu , Guangyong Chen , Dehao Yang

{"title":"The role of the immune system in Parkinson's disease pathogenesis: A focus on Th17 cells - A systematic review and meta-analysis","authors":"Zihan Jiang , Honghao Huang , Yiqun Chen , Haobo Xie , Yangguang Lu , Yaoyin Ge , Ruotong Yao , Lingsheng Wang , Zihao Wu , Yiran Bu , Guangyong Chen , Dehao Yang","doi":"10.1016/j.jneuroim.2024.578484","DOIUrl":"10.1016/j.jneuroim.2024.578484","url":null,"abstract":"<div><h3>Background</h3><div>Parkinson's disease (PD) has been linked to T helper 17 (Th17) cells in prior investigations, but the evidence remains inconclusive. To gain a deeper understanding of this potential connection, we conducted a systematic review and meta-analysis.</div></div><div><h3>Methods</h3><div>A comprehensive search for relevant studies published up to July 8, 2023, was performed across PubMed, EMBASE, and Cochrane Library databases. A random-effect model was employed to synthesize effect sizes and their corresponding 95 % confidence intervals (CIs). Leave-one-out sensitivity analysis and funnel plots with trim-and-fill were utilized to assess the combined results' robustness.</div></div><div><h3>Results</h3><div>Thirteen studies were ultimately included in the meta-analysis. Pooled effect sizes indicated a significantly higher percentage of Th17 cells in PD patients (Standardized Mean Difference [SMD] = 1.00, 95 % CI 0.30–1.71). Notably, Th17 cell levels were more elevated in Asian PD patients (SMD = 1.33, 95 % CI 0.31–2.35). Additionally, the percentage of Th17 cells positively correlated with Movement Disorder Society Unified Parkinson's Disease Rating Scale-III (UPDRS-III) scores (<em>r</em> = 0.22, 95 % CI 0.01–0.41), indicating a link to motor dysfunction. Conversely, a negative correlation was observed with Cognitive function scale scores (<em>r</em> = − 0.27, 95 % CI -0.47–-0.04), suggesting a potential association with cognitive decline.</div></div><div><h3>Conclusions</h3><div>This study revealed a positive association between Th17 cells and PD, with PD patients exhibiting elevated Th17 levels. Furthermore, the percentage of Th17 cells correlated with motor and cognitive impairments in PD patients.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"398 ","pages":"Article 578484"},"PeriodicalIF":2.9,"publicationDate":"2024-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142692404","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

Immune cell-enriched single-cell RNA sequencing unveils the interplay between infiltrated CD8+ T resident memory cells and choroid plexus epithelial cells in Alzheimer's disease 免疫细胞富集单细胞 RNA 测序揭示了阿尔茨海默病中浸润的 CD8+ T 常驻记忆细胞与脉络丛上皮细胞之间的相互作用。

IF 2.9 4区医学

Journal of neuroimmunology Pub Date : 2024-11-17 DOI: 10.1016/j.jneuroim.2024.578488

Seong-Jun Kang , Yong-Hee Kim , Thuy Nguyen-Phuong , Yijoon Kim , Jin-Mi Oh , Jae-chun Go , DaeSik Kim , Chung-Gyu Park , Hyunsu Lee , Hyun Je Kim

{"title":"Immune cell-enriched single-cell RNA sequencing unveils the interplay between infiltrated CD8+ T resident memory cells and choroid plexus epithelial cells in Alzheimer's disease","authors":"Seong-Jun Kang , Yong-Hee Kim , Thuy Nguyen-Phuong , Yijoon Kim , Jin-Mi Oh , Jae-chun Go , DaeSik Kim , Chung-Gyu Park , Hyunsu Lee , Hyun Je Kim","doi":"10.1016/j.jneuroim.2024.578488","DOIUrl":"10.1016/j.jneuroim.2024.578488","url":null,"abstract":"<div><div>Alzheimer's disease (AD) is a progressive neurological disorder and the leading cause of dementia. Despite significant efforts, treatment strategies targeting amyloid-β have been less successful than anticipated. Recently, the role of neuroinflammation and adaptive immune response in AD pathogenesis has gained attention. Here, we performed immune cell-enriched single-cell RNA sequencing of brain parenchymal cells from 12-month-old 5xFAD, an AD mouse model. We analyzed 11,587 single cells and found distinct differences in T cell and choroid plexus cell populations between 5xFAD mouse and littermate control. Subsequent sub-clustering of T cells in the 5xFAD mouse revealed distinct subtypes, with CD8<sup>+</sup> resident memory T cells (T<sub>RM</sub>) being the most prevalent T cell type. In addition, we observed an increase in T cell exhaustion markers, including <em>Pdcd1, Ctla4, and Havcr2</em>, with a particularly significant elevation of PD-1 and TIM-3 in CD8<sup>+</sup> T<sub>RM</sub> in 5xFAD mouse. Furthermore, choroid plexus (ChP) epithelial cells showed altered gene expression patterns, with higher expression of MHC class I and Type I IFN-stimulated genes in 5xFAD mouse compared to the control mouse, suggesting an association with clonal expansion of AD-specific T cells in the brain. Through single-cell RNA sequencing (scRNA-seq) analysis, our study highlights the potential role of resident memory CD8<sup>+</sup> T cell and their possible interactions with ChP epithelial cells. This study provides an exploration of the brain microenvironment landscape in AD, revealing critical insights into its underlying mechanisms.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"398 ","pages":"Article 578488"},"PeriodicalIF":2.9,"publicationDate":"2024-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142687200","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