Journal of neuroimmunology最新文献

{"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 ,&nbsp;Yong-Hee Kim ,&nbsp;Thuy Nguyen-Phuong ,&nbsp;Yijoon Kim ,&nbsp;Jin-Mi Oh ,&nbsp;Jae-chun Go ,&nbsp;DaeSik Kim ,&nbsp;Chung-Gyu Park ,&nbsp;Hyunsu Lee ,&nbsp;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⁺ resident memory T cells (T_RM) 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⁺ T_RM 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⁺ 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}

{"title":"Retinoic acid modulates peripheral blood helper innate lymphoid cell composition in vitro in patients with multiple sclerosis","authors":"Altuğ Özkoşar ,&nbsp;Fatma Betül Öktelik ,&nbsp;Metin Yusuf Gelmez ,&nbsp;Sevda Öztürk Erden ,&nbsp;Tuncay Gündüz ,&nbsp;Murat Kürtüncü ,&nbsp;Günnur Deniz ,&nbsp;Suzan Çınar","doi":"10.1016/j.jneuroim.2024.578489","DOIUrl":"10.1016/j.jneuroim.2024.578489","url":null,"abstract":"<div><div>This study investigates the frequency and numbers of circulating helper innate lymphoid cells (ILCs) in untreated relapsing-remitting multiple sclerosis (RRMS) patients, focusing on intracellular IL-10 and CCR6 expressions under IL-2, IL-33, and retinoic acid (RA) stimulation <em>in vitro</em> and their associations with clinical features in RRMS. In RRMS patients, ILC1 levels were notably higher upon IL-2 + IL-33 + RA stimulation, while ILC2 levels, particularly the c-Kit⁺ ILC2 and CCR6⁺ ILC2 subsets, were significantly lower compared to unstimulated conditions. Additionally, IL-10⁺ ILC1 levels were elevated. The ratios of IL-10⁺ ILC1/ILC1, c-Kit⁺ ILC2/c-Kit⁻ ILC2, and CCR6⁺ ILC2/ILC2 were associated with the progression index (PI) in RRMS patients.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"398 ","pages":"Article 578489"},"PeriodicalIF":2.9,"publicationDate":"2024-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142710564","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}

{"title":"Silencing of circular RNA PTP4A2 ameliorates depressive-like behaviors by inhibiting microglia activation in mice","authors":"Han Zhang,&nbsp;Xiang Chen,&nbsp;Jialu Qian","doi":"10.1016/j.jneuroim.2024.578486","DOIUrl":"10.1016/j.jneuroim.2024.578486","url":null,"abstract":"<div><div>Major depressive disorder (MDD) is a prevalent mental illness and showed a strong link with inflammation. Microglia, as the main resident immune cells, play an important role in the occurrence and development of depression. Circular RNA PTP4A2 (circPTP4A2) was highly expressed in microglia inflammation induced by oxygen glucose deprivation/reperfusion. However, whether circPTP4A2 involves in microglia inflammation in MDD is not clear. Here, chronic unpredictable stress (CUS) induced depressive behaviors and microglia activation in mouse hippocampus, accompanied by the elevated expression of circPTP4A2. Knockdown circPTP4A2 in mouse hippocampus ameliorated depressive-like behaviors and microglia activation. Moreover, CUS promoted phosphorylation of ERK, JNK and P38 in mouse hippocampus as same as LPS-exposed BV2 microglia. Only P38 phosphorylation was inhibited by circPTP4A2 knockdown in the hippocampus. P38 inhibitor, sb203580, repressed circPTP4A2 overexpression-induced inflammatory reaction in BV2 cells. These findings suggest that circPTP4A2 promotes depressive-like behaviors and microglia activation via P38 phosphorylation.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"397 ","pages":"Article 578486"},"PeriodicalIF":2.9,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142643786","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}

{"title":"Pre-existing Lambert-Eaton Myasthenic Syndrome and Scleroderma in a Patient with Neuroendocrine Carcinoma Undergoing Immune Checkpoint Inhibitor Cancer Immunotherapy","authors":"Nisa Vorasoot ,&nbsp;Thorvardur R. Halfdanarson ,&nbsp;Nicolas N. Madigan ,&nbsp;Divyanshu Dubey ,&nbsp;Uma Thanarajasingam ,&nbsp;Anastasia Zekeridou","doi":"10.1016/j.jneuroim.2024.578485","DOIUrl":"10.1016/j.jneuroim.2024.578485","url":null,"abstract":"<div><h3>Introduction</h3><div>Paraneoplastic neurological syndromes (PNS) can worsen with immune checkpoint inhibitor (ICI) cancer immunotherapy.</div></div><div><h3>Case report</h3><div>A 66-year-old female with paraneoplastic Lambert-Eaton Myasthenic Syndrome (LEMS), which led to the diagnosis of metastatic neuroendocrine carcinoma, was treated with intravenous immune globulin (IVIg) (with minimal response), chemotherapy, and radiation, resulting in neurological improvement. However, sclerodermatous changes developed after a year. Due to cancer progression, dual ICI therapy was initiated, and the patient remained stable for eight months until the progression of both LEMS and cancer, ultimately leading to death.</div></div><div><h3>Discussion</h3><div>This case highlights the challenges of managing pre-existing PNS during ICI therapy, emphasizing the need for a multidisciplinary approach and the consideration of unusual clinical presentations in therapeutic decision-making.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"398 ","pages":"Article 578485"},"PeriodicalIF":2.9,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142695524","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}

{"title":"MOGAD presenting as fulminant intracranial hypertension","authors":"Sai Nagaratnam ,&nbsp;Amardeep Gill ,&nbsp;Niroshan Jeyakumar ,&nbsp;Shuo Xi ,&nbsp;Ming-Wei Lin ,&nbsp;Andrew Martin ,&nbsp;Winny Varikatt ,&nbsp;Michael W.K. Fong ,&nbsp;Hugo Morales-Briceno","doi":"10.1016/j.jneuroim.2024.578487","DOIUrl":"10.1016/j.jneuroim.2024.578487","url":null,"abstract":"<div><h3>Objectives</h3><div>Myelin oligodendrocyte glycoprotein antibody disease (MOGAD) has an expanding phenotype. We describe two cases of MOGAD with associated severe intracranial hypertension.</div><div>Case 1: A 21-year-old male presented with diffuse cortical encephalitis and intracranial hypertension with both serum and CSF MOG antibody positivity. Initial brain CT scan was normal but subsequent demyelination was evident on MRI. Case 2: A 44-year-old female presented with a progressive brainstem encephalitis and intracranial hypertension and normal MRI, with later development of subcortical demyelination which was confirmed on brain biopsy. CSF-restricted MOG antibody was detected following the biopsy results.</div></div><div><h3>Results</h3><div>Both patients presented with clinical features of severe intracranial hypertension requiring surgical management followed by immunosuppressive therapy (methylprednisone and plasma exchange; and intravenous immunoglobulin and plasma exchange) leading to clinical improvement.</div></div><div><h3>Discussion</h3><div>MOGAD should be in the differential diagnosis of acute severe intracranial hypertension even in the absence of demyelination on initial neuroimaging. Clinicians should be alert of this syndrome that requires combined management of intracranial pressure in addition to early and intensive immunotherapy.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"397 ","pages":"Article 578487"},"PeriodicalIF":2.9,"publicationDate":"2024-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142639222","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}

{"title":"Minocycline inhibits microglial activation in the CA1 hippocampal region and prevents long-term cognitive sequel after experimental cerebral malaria","authors":"E.T. Moreira ,&nbsp;M.P. Lourenço ,&nbsp;T. Cunha-Fernandes ,&nbsp;T.I. Silva ,&nbsp;L.D. Siqueira ,&nbsp;H.C. Castro-Faria-Neto ,&nbsp;P.A. Reis","doi":"10.1016/j.jneuroim.2024.578480","DOIUrl":"10.1016/j.jneuroim.2024.578480","url":null,"abstract":"<div><div>Cerebral malaria is the worst complication of malaria infection, has a high mortality rate, and may cause different neurodysfunctions, including cognitive decline. Neuroinflammation is an important cause of cognitive damage in neurodegenerative diseases, and microglial cells can be activated in a disease-associated profile leading to tissue damage and neuronal death. Here, we demonstrated that treatment with minocycline reduced blood-brain barrier breakdown and modulated ICAM1 mRNA expression; reduced proinflammatory cytokines, such as TNF-α, IL-1β, IFN-γ, and IL-6; and prevented long-term cognitive decline in contextual and aversive memory tasks. Taken together, our data suggest that microglial cells are activated during experimental cerebral malaria, leading to neuroinflammatory events that end up in cognitive damage. In addition, pharmacological modulation of microglial activation, by drugs such as minocycline may be an important therapeutic strategy in the prevention of long-term memory impairment.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"397 ","pages":"Article 578480"},"PeriodicalIF":2.9,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142586463","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}

{"title":"Influence of cocaine use reduction on markers of immune function","authors":"William W. Stoops ,&nbsp;Thomas P. Shellenberg ,&nbsp;Sean D. Regnier ,&nbsp;David H. Cox ,&nbsp;Reuben Adatorwovor ,&nbsp;Lon R. Hays ,&nbsp;Danielle M. Anderson ,&nbsp;Joshua A. Lile ,&nbsp;Joy M. Schmitz ,&nbsp;Jennifer R. Havens ,&nbsp;Suzanne C. Segerstrom","doi":"10.1016/j.jneuroim.2024.578470","DOIUrl":"10.1016/j.jneuroim.2024.578470","url":null,"abstract":"<div><div>This study determined the effects of reduced cocaine use on immune function. Treatment seeking participants with Cocaine Use Disorder enrolled in a 12-week contingency management trial to reduce cocaine use. Participants were randomly assigned 1:1:1 to High Value Reinforcers (i.e., $55/negative urine sample) for cocaine abstinence (<em>n</em> = 41), Low Value Reinforcers (i.e., $13/negative urine sample) for cocaine abstinence (<em>n</em> = 33) or Non-Contingent Control (n = 33). Immune measures were collected at 6-week intervals. The High Value group had greatest use reductions, increased erythema and IL-6 and decreased IL-10 and CCL5, suggesting an activated immune response. Cocaine use reduction may promote changes in immune health.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"397 ","pages":"Article 578470"},"PeriodicalIF":2.9,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142590665","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}

{"title":"Kidney injury: An overlooked manifestation in autoimmune encephalitis","authors":"Zhirong Fan ,&nbsp;Jing Li ,&nbsp;Yingchi Zhang ,&nbsp;Juan Kang ,&nbsp;Di Wang ,&nbsp;Lijuan Liu ,&nbsp;Min Li ,&nbsp;Xiaodan Shi ,&nbsp;Na Yuan ,&nbsp;Yuanli Zhang ,&nbsp;Fang Du ,&nbsp;Wen Jiang","doi":"10.1016/j.jneuroim.2024.578472","DOIUrl":"10.1016/j.jneuroim.2024.578472","url":null,"abstract":"<div><h3>Aim</h3><div>To investigate the prevalence and clinical features of kidney injury in patients with autoimmune encephalitis (AE).</div></div><div><h3>Methods</h3><div>Kidney injury was suspected in kidney-involving group due to persistent abnormal in urinary protein and serum albumin. Data on demographics and clinical features were compared between kidney-involving group and kidney-sparing group (patients without kidney injury) using Wilcoxon rank-sum test or chi-square test. Renal biopsy was conducted to identify the type of kidney injury.</div></div><div><h3>Results</h3><div>Approximate 30 % (32 of 108) patients with AE were suspicious of kidney injury. Nine patients further tested 24 h urine total protein, and seven of them had an elevated urine protein higher than 150 mg. The predominantly patterns of kidney injury were elevated urine protein, decreased serum albumin and normal kidney function. Compared to kidney-sparing group, the spectrum of AE antibodies in kidney-involving group was different, manifested as less anti-<em>N</em>-methyl-<span>d</span>-aspartate receptor antibodies (50 % vs. 72.4 %, <em>p</em> = 0.025) and more anti-contactin-associated protein like 2 antibodies (18.8 % vs. 1.3 %, <em>p</em> = 0.003). Definite pathological changes indicative of IgA nephropathy and membranous nephropathy in renal biopsy of two cases provided evidence of autoimmune attacks.</div></div><div><h3>Discussion</h3><div>Kidney injury occurred in considerable proportion of patients with AE. An in-depth screening for nephropathy could be essential for AE.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"397 ","pages":"Article 578472"},"PeriodicalIF":2.9,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142561070","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}

{"title":"Corrigendum to “Clinical features and outcomes of patients with muscle-specific kinase antibody-positive myasthenia gravis in Japan” [Journal of Neuroimmunology 385 (2023) 578241].","authors":"Manato Yasuda ,&nbsp;Akiyuki Uzawa ,&nbsp;Satoshi Kuwabara ,&nbsp;Shigeaki Suzuki ,&nbsp;Hiroyuki Akamine ,&nbsp;Yosuke Onishi ,&nbsp;Yukiko Ozawa ,&nbsp;Naoki Kawaguchi ,&nbsp;Tomoya Kubota ,&nbsp;Masanori P. Takahashi ,&nbsp;Yasushi Suzuki ,&nbsp;Genya Watanabe ,&nbsp;Takashi Kimura ,&nbsp;Takamichi Sugimoto ,&nbsp;Makoto Samukawa ,&nbsp;Naoya Minami ,&nbsp;Masayuki Masuda ,&nbsp;Shingo Konno ,&nbsp;Yuriko Nagane ,&nbsp;Kimiaki Utsugisawa","doi":"10.1016/j.jneuroim.2024.578465","DOIUrl":"10.1016/j.jneuroim.2024.578465","url":null,"abstract":"","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"397 ","pages":"Article 578465"},"PeriodicalIF":2.9,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142502427","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}

{"title":"Modulating sonic hedgehog (SHH) pathway to create a rapid CNS-TB model: Facilitating drug discovery","authors":"Mohamad Mosa Mubarak ,&nbsp;Shahnawaz Majeed ,&nbsp;Zubair Ahmad Wani ,&nbsp;Hadiya Amin Kantroo ,&nbsp;Abbass Malik ,&nbsp;Ishfaq Ahmad Baba ,&nbsp;Radhika Mhatre ,&nbsp;Zahoor Ahmad","doi":"10.1016/j.jneuroim.2024.578471","DOIUrl":"10.1016/j.jneuroim.2024.578471","url":null,"abstract":"<div><div>Tuberculous meningitis, a severe complication of <em>Mycobacterium tuberculosis</em> (<em>M. tb</em>) infection, involves the dissemination of bacilli in the brain. This study explored the role of the sonic hedgehog (SHH) signaling pathway in regulating blood-brain barrier (BBB) integrity, <em>M. tb</em> invasion into the central nervous system (CNS), and disease progression of Central Nervous System Tuberculosis (CNS-TB) in a Balb/c mouse model. The modulation of the SHH pathway using agonist Purmorphamine (PUR) and antagonist Cyclopamine (CYC) revealed that CYC treatment led to a rapid and extensive invasion of <em>M. tb</em> in the brain, with bacterial loads increasing by 99 % compared to the untreated-infected group. In contrast, PUR reduced <em>M. tb</em> loads by 50 % and delayed disease progression. Histopathological analysis showed that CYC exacerbated inflammation and immune cell infiltration, while PUR mitigated these responses. Immunohistochemistry demonstrated that CYC caused severe BBB breakdown and reactive gliosis, while PUR partially attenuated this response. Further analysis revealed that CYC upregulated Matrix Metalloproteinase-9 (MMP-9) secretion, a key contributor to BBB disruption. These findings highlight the critical role of the SHH pathway in maintaining BBB integrity and regulating the immunopathological response during CNS-TB, opening up future scope for drug discovery. This Cyclopamine-induced model of rapid <em>M. tb</em> invasion and chronic inflammation provides a new tool for studying CNS-TB pathogenesis and evaluating potential therapeutic interventions targeting the SHH signaling axis.</div></div><div><h3>Significance statement</h3><div>Understanding how tuberculosis (TB) infection can spread to the brain is crucial, as this “central nervous system TB” (CNS-TB) is a serious and potentially life-threatening health complication. However, studying CNS-TB in humans is very difficult. Animal models are needed to better understand how TB gets into the brain and the resulting damage. This study in mice showed that blocking a signaling pathway called Sonic Hedgehog (SHH) allowed TB to rapidly spread to the brain, damaging the blood-brain barrier and causing severe inflammation. In contrast, activating the SHH pathway helped protect the brain from TB. These findings provide important insights that could lead to new ways to prevent or treat this dangerous form of TB.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"397 ","pages":"Article 578471"},"PeriodicalIF":2.9,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142622542","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}