Journal of neuroimmunology最新文献

{"title":"Aflatoxin B1 exposure deteriorates immune abnormalities in a BTBR T+ Itpr3tf/J mouse model of autism by increasing inflammatory mediators' production in CD19-expressing cells","authors":"Taghreed N. Almanaa ,&nbsp;Mohammad Y. Alwetaid ,&nbsp;Saleh A. Bakheet ,&nbsp;Sabry M. Attia ,&nbsp;Mushtaq A. Ansari ,&nbsp;Ahmed Nadeem ,&nbsp;Sheikh F. Ahmad","doi":"10.1016/j.jneuroim.2024.578365","DOIUrl":"https://doi.org/10.1016/j.jneuroim.2024.578365","url":null,"abstract":"<div><p>Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by deficiencies in communication, repetitive and stereotyped behavioral patterns, and difficulties in reciprocal social engagement. The presence of immunological dysfunction in ASD has been well established. Aflatoxin B₁ (AFB₁) is a prevalent mycotoxin found in food and feed, causing immune toxicity and hepatotoxicity. AFB₁ is significantly elevated in several regions around the globe. Existing research indicates that prolonged exposure to AFB₁ results in neurological problems. The BTBR T⁺ Itpr3^tf/J (BTBR) mice, which were used as an autism model, exhibit the primary behavioral traits that define ASD, such as repeated, stereotyped behaviors and impaired social interactions. The main objective of this work was to assess the toxic impact of AFB₁ in BTBR mice. This work aimed to examine the effects of AFB₁ on the expression of Notch-1, IL-6, MCP-1, iNOS, GM-CSF, and NF-κB p65 by CD19⁺ B cells in the spleen of the BTBR using flow cytometry. We also verified the impact of AFB₁ exposure on the mRNA expression levels of Notch-1, IL-6, MCP-1, iNOS, GM-CSF, and NF-κB p65 in the brain of BTBR mice using real-time PCR. The findings of our study showed that the mice treated with AFB₁ in the BTBR group exhibited a substantial increase in the presence of CD19⁺Notch-1⁺, CD19⁺IL-6⁺, CD19⁺MCP-1⁺, CD19⁺iNOS⁺, CD19⁺GM-CSF⁺, and CD19⁺NF-κB p65⁺ compared to the mice in the BTBR group that were treated with saline. Our findings also confirmed that administering AFB₁ to BTBR mice leads to elevated mRNA expression levels of Notch-1, IL-6, MCP-1, iNOS, GM-CSF, and NF-κB p65 in the brain, in comparison to BTBR mice treated with saline. The data highlight that exposure to AFB₁ worsens immunological abnormalities by increasing the expression of inflammatory mediators in BTBR mice.</p></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"391 ","pages":"Article 578365"},"PeriodicalIF":3.3,"publicationDate":"2024-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140894054","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":"Immune dysregulation in chronic inflammatory demyelinating polyneuropathy","authors":"Yingkai Li ,&nbsp;John S. Yi ,&nbsp;Jeffrey T. Guptill ,&nbsp;Vern C. Juel ,&nbsp;Lisa Hobson-Webb ,&nbsp;Shruti M. Raja ,&nbsp;Tabitha Karatz ,&nbsp;Karissa L. Gable","doi":"10.1016/j.jneuroim.2024.578360","DOIUrl":"https://doi.org/10.1016/j.jneuroim.2024.578360","url":null,"abstract":"<div><h3>Objective</h3><p>Chronic inflammatory demyelinating polyneuropathy (CIDP) is an autoimmune disorder of the peripheral nerves with an incompletely understood underlying pathophysiology. This investigation focused on defining B and T cell frequencies, T cell functional capacity and innate immune system analysis in patients with CIDP.</p></div><div><h3>Methods</h3><p>By using multi-parameter flow cytometry, we examined the phenotype and function of PBMCs in 25 CIDP patients who were relatively clinically stable on treatment who met EFNS/PNS criteria, 21 patients with genetically confirmed hereditary neuropathy and 25 healthy controls. We also evaluated the regulatory T cell (Treg) inhibitory capacity by co-culturing Treg and effector T cells.</p></div><div><h3>Results</h3><p>Proinflammatory CD4 T cells, especially type 1 helper T cell (Th1) and CD8 T cells in patients with CIDP were found to have an enhanced capacity to produce inflammatory cytokines. There was no difference in frequency of Th17 regulatory cells in CIDP patients versus healthy controls, however, Treg function was impaired in CIDP patients. There was no remarkable difference in innate immune system measures. Within B cell subsets, transitional cell frequency was decreased in CIDP patients.</p></div><div><h3>Interpretation</h3><p>Patients with CIDP clinically stable on treatment continued to show evidence of a proinflammatory state with impaired Treg function. This potentially implies an inadequate suppression of ongoing inflammation not addressed by standard of care therapies as well as persistent activity of disease while on treatment. Targeting T cells, especially inhibiting Th1 and polyfunctional CD8 T cells or improving Treg cell function could be potential targets for future therapeutic research.</p></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"391 ","pages":"Article 578360"},"PeriodicalIF":3.3,"publicationDate":"2024-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140894055","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":"Mitigation of CXCL10 secretion by metabolic disorder drugs in microglial-mediated neuroinflammation","authors":"Sophia F. Oliai ,&nbsp;Daniel C. Shippy ,&nbsp;Tyler K. Ulland","doi":"10.1016/j.jneuroim.2024.578364","DOIUrl":"https://doi.org/10.1016/j.jneuroim.2024.578364","url":null,"abstract":"<div><p>Metabolic disorders are associated with several neurodegenerative diseases. We previously identified C-X-C motif chemokine ligand 10 (CXCL10), also known as interferon gamma-induced protein 10 (IP-10), as a major contributor to the type I interferon response in microglial-mediated neuroinflammation. Therefore, we hypothesized FDA-approved metabolic disorder drugs that attenuate CXCL10 secretion may be repurposed as a treatment for neurodegenerative diseases. Screening, dose curves, and cytotoxicity assays in LPS-stimulated microglia yielded treprostinil (hypertension), pitavastatin (hyperlipidemia), and eplerenone (hypertension) as candidates that significantly reduced CXCL10 secretion (in addition to other pro-inflammatory mediators) without impacting cell viability. Altogether, these data suggest metabolic disorder drugs that attenuate CXCL10 as potential treatments for neurodegenerative disease through mitigating microglial-mediated neuroinflammation.</p></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"391 ","pages":"Article 578364"},"PeriodicalIF":3.3,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140843296","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":"Endothelial dysfunction in neurodegenerative disease: Is endothelial inflammation an overlooked druggable target?","authors":"Megan Ritson,&nbsp;Caroline P.D. Wheeler-Jones,&nbsp;Helen B. Stolp","doi":"10.1016/j.jneuroim.2024.578363","DOIUrl":"https://doi.org/10.1016/j.jneuroim.2024.578363","url":null,"abstract":"<div><p>Neurological diseases with a neurodegenerative component have been associated with alterations in the cerebrovasculature. At the anatomical level, these are centred around changes in cerebral blood flow and vessel organisation. At the molecular level, there is extensive expression of cellular adhesion molecules and increased release of pro-inflammatory mediators. Together, these has been found to negatively impact blood-brain barrier integrity. Systemic inflammation has been found to accelerate and exacerbate endothelial dysfunction, neuroinflammation and degeneration. Here, we review the role of cerebrovasculature dysfunction in neurodegenerative disease and discuss the potential contribution of intermittent pro-inflammatory systemic disease in causing endothelial pathology, highlighting a possible mechanism that may allow broad-spectrum therapeutic targeting in the future.</p></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"391 ","pages":"Article 578363"},"PeriodicalIF":3.3,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S016557282400081X/pdfft?md5=94631cc6d2525fa33a9beb69ac72188b&pid=1-s2.0-S016557282400081X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140894057","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":"Causal association between multiple sclerosis and severe COVID-19: A bidirectional Mendelian randomization study","authors":"Shuangjie Li ,&nbsp;Dongren Sun ,&nbsp;Rui Wang,&nbsp;Qin Du,&nbsp;Hongxi Chen,&nbsp;Ziyan Shi,&nbsp;Hongyu Zhou","doi":"10.1016/j.jneuroim.2024.578352","DOIUrl":"https://doi.org/10.1016/j.jneuroim.2024.578352","url":null,"abstract":"","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"391 ","pages":"Article 578352"},"PeriodicalIF":3.3,"publicationDate":"2024-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140822044","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":"Unilateral cortical autoimmune encephalitis: A case series and comparison to late-onset Rasmussen's encephalitis","authors":"Sophia Damman ,&nbsp;Persen Sukpornchairak ,&nbsp;Amit Ahituv ,&nbsp;Alex Chen ,&nbsp;David Wang ,&nbsp;Komal Sawlani ,&nbsp;Claude Steriade ,&nbsp;Hesham Abboud","doi":"10.1016/j.jneuroim.2024.578350","DOIUrl":"https://doi.org/10.1016/j.jneuroim.2024.578350","url":null,"abstract":"<div><h3>Objective</h3><p>To report a novel anatomical pattern of autoimmune encephalitis characterized by strictly unilateral cortical inflammation and a clinical picture overlapping with late-onset Rasmussen's encephalitis.</p></div><div><h3>Methods</h3><p>We retrospectively gathered data of patients identified at two tertiary referral academic centers who met inclusion criteria.</p></div><div><h3>Results</h3><p>We identified twelve cases (average age 65, +/− 19.8 years, 58% female). All patients had unilateral cortical inflammation manifesting with focal seizures, cognitive decline, hemicortical deficits, and unilateral MRI and/or EEG changes. Six cases were idiopathic, two paraneoplastic, two iatrogenic (in the setting of immune checkpoint inhibitors), and two post-COVID-19. Serologically, ten patients were seronegative, one had high titer anti-GAD65, and one had anti-NMDAR. Five patients met Rasmussen's encephalitis criteria, and six did not fully meet the criteria but had symptoms significantly overlapping with the condition. Most patients had significant improvement with immunotherapy.</p></div><div><h3>Discussion</h3><p>Unilateral cortical AE seems to be more prevalent in the elderly and more frequently idiopathic and seronegative. Patients with this anatomical variant of autoimmune encephalitis have overlapping features with late-onset Rasmussen's encephalitis but are more responsive to immunotherapy. In cases refractory to immunotherapy, interventions used in refractory Rasmussen's encephalitis may be considered, such as functional hemispherectomy.</p></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"391 ","pages":"Article 578350"},"PeriodicalIF":3.3,"publicationDate":"2024-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140894056","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":"A protective effect of lower MHC-II expression in MOGAD","authors":"Ariel Rechtman,&nbsp;Omri Zveik,&nbsp;Nitsan Haham,&nbsp;Livnat Brill ,&nbsp;Adi Vaknin-Dembinsky","doi":"10.1016/j.jneuroim.2024.578351","DOIUrl":"https://doi.org/10.1016/j.jneuroim.2024.578351","url":null,"abstract":"<div><p>Myelin oligodendrocyte glycoprotein-antibody-associated disease (MOGAD) is a demyelinating central nervous system disorder. We aimed to uncover immune pathways altered in MOGAD to predict disease progression. Using nanostring nCounter technology, we analyzed immune gene expression in PBMCs from MOGAD patients and compare it with healthy controls (HCs). We found 35 genes that distinguished MOGAD patients and HCs. We then validated those results in a larger cohort including MS and NMOSD patients. Expressions of HLA-DRA was significantly lower in MOGAD patients. This reduction in HLA-DRA, correlated with a monophasic disease course and greater brain volume, enhancing our ability to predict MOGAD progression.</p></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"391 ","pages":"Article 578351"},"PeriodicalIF":3.3,"publicationDate":"2024-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140822043","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":"Atractylodin ameliorates lipopolysaccharide-induced depressive-like behaviors in mice through reducing neuroinflammation and neuronal damage","authors":"Feng Liu,&nbsp;Yaping Wang,&nbsp;Dongbo Li,&nbsp;Tao Yang","doi":"10.1016/j.jneuroim.2024.578349","DOIUrl":"https://doi.org/10.1016/j.jneuroim.2024.578349","url":null,"abstract":"<div><p>Depression is a psychiatric disorder associated with multiple factors including microglia-mediated neuroinflammation. Although atractylodin exerted a variety of biological activities, however the effect of atractylodin on neuroinflammation-related depression was still unclear. In this study, the lipopolysaccharide (LPS)-induced mouse model was used to explore the antidepressant effects and molecular mechanisms of atractylodin. The results showed that atractylodin increased sugar preference, also reduced immobility time in FST and TST. Further study showed atractylodin reduced the oxidative stress and the activation of microglia in mouse hippocampus, also inhibited the level of cytokine release, especially IL-1β. The results of western blotting showed that atractylodin significantly inhibited the expression of NLRP3 and pro-IL1β <em>via</em> inhibition of NF-κB pathway. Our studies showed that atractylodin upregulated BDNF/Akt pathway in mouse hippocampus. Therefore, this study firstly indicated that atractylodin can ameliorate lipopolysaccharide-induced depressive-like behaviors in mice through reducing neuroinflammation and neuronal damage, and its molecular mechanism may be associated with the decrease of the expression of NLRP3 inflammasome and upregulation of BDNF/Akt pathway.</p></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"390 ","pages":"Article 578349"},"PeriodicalIF":3.3,"publicationDate":"2024-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140647508","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":"Superior oblique palsy as the initial manifestation of anti-contactin-1 IgG4 autoimmune nodopathy: A case report","authors":"Young Gi Min ,&nbsp;Woohee Ju ,&nbsp;Jung-Joon Sung","doi":"10.1016/j.jneuroim.2024.578348","DOIUrl":"10.1016/j.jneuroim.2024.578348","url":null,"abstract":"<div><p>Autoimmune nodopathy (AN) is a group of peripheral neuropathies caused by antibodies targeting the nodes of Ranvier or paranodes. It typically presents with sensory ataxia, distal limb weakness, and tremor, and often has a subacute onset, with limited response to immunoglobulin or corticosteroids. We report a case of anti-contactin-1 neuropathy initially manifesting as isolated superior oblique palsy, aiming to broaden the clinical spectrum of the disease. A 68-year-old male with well-controlled diabetes, hypertension, and hyperlipidemia developed acute binocular vertical diplopia, progressing over two months to include distal paresthesia, sensory ataxia, ageusia, and dysarthria. Concurrent nephrotic syndrome was identified. Nerve conduction studies supported demyelination. Despite treatment with intravenous methylprednisolone followed by long-term immunosuppression, some disability persisted. Serum archived during his admission tested positive for anti-contactin-1 IgG, with IgG4 as the predominant subclass, in the flow cytometry assay for AN. This case extends the clinical spectrum of AN. Some cases of isolated cranial nerve palsies, especially in the relevant context like nephrotic syndrome, may be attributed to AN. Prompt initiation of more effective therapies, such as rituximab, could significantly improve outcomes.</p></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"391 ","pages":"Article 578348"},"PeriodicalIF":3.3,"publicationDate":"2024-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140759426","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":"Antigen-specific immunotherapy via delivery of tolerogenic dendritic cells for multiple sclerosis","authors":"Vivien Li ,&nbsp;Michele D. Binder ,&nbsp;Anthony W. Purcell ,&nbsp;Trevor J. Kilpatrick","doi":"10.1016/j.jneuroim.2024.578347","DOIUrl":"https://doi.org/10.1016/j.jneuroim.2024.578347","url":null,"abstract":"<div><p>Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system resulting from loss of immune tolerance. Many disease-modifying therapies for MS have broad immunosuppressive effects on peripheral immune cells, but this can increase risks of infection and attenuate vaccine-elicited immunity. A more targeted approach is to re-establish immune tolerance in an autoantigen-specific manner. This review discusses methods to achieve this, focusing on tolerogenic dendritic cells. Clinical trials in other autoimmune diseases also provide learnings with regards to clinical translation of this approach, including identification of autoantigen(s), selection of appropriate patients and administration route and frequency.</p></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"390 ","pages":"Article 578347"},"PeriodicalIF":3.3,"publicationDate":"2024-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140644523","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}