Journal of neuroimmunology最新文献

{"title":"The immunology and neuropathology of the autoimmune nodopathies","authors":"Claire Bergstrom Johnson ,&nbsp;Janev Fehmi ,&nbsp;Simon Rinaldi","doi":"10.1016/j.jneuroim.2025.578665","DOIUrl":"10.1016/j.jneuroim.2025.578665","url":null,"abstract":"<div><div>The autoimmune nodopthies have recently emerged as a discrete subtype of inflammatory neuropathy. They are characterised by the presence of IgG class autoantibodies directed against structural components of the node of Ranvier, such as the axonal isoform of neurofascin (NF186), or flanking paranodes, where NF155, on the glial membrane, and the axonal complex of contactin-1 and contactin-associated protein-1 (Caspr1), are established targets. Although initially proposed to be atypical forms of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), many patients initially present with a clinical picture in keeping with the acute inflammatory neuropathy Guillain-Barré syndrome (GBS). Furthermore, compared to seronegative CIDP and GBS, the autoimmune nodopathies have distinct underlying immunological and neuropathogenic mechanisms. Crucially, the treatment response profile is also different, and patients often fail to respond to immunotherapies typically used in seronegative cases, such as immunoglobulin infusions and corticosteroids. However, responses to anti-CD20 B-cell depleting therapies are frequent and often long-lasting. This review provides on overview of the antigenic landscape of the node of Ranvier, and the broad concept of nodopathies, and summarises the immunology, neuropathology and clinical features of these disabling yet treatable disorders.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"406 ","pages":"Article 578665"},"PeriodicalIF":2.9,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144263652","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":"Autoimmune encephalitis and delayed diagnosis in common variable immunodeficiency: A case report and review of literature","authors":"Mastooreh Sagharichi ,&nbsp;Mohammad Amin Aalipour ,&nbsp;Elahe Eghbal ,&nbsp;Farid Javandoust Gharehbagh ,&nbsp;Roozbe Shadidi Asil ,&nbsp;Ilad Alavi Darazam","doi":"10.1016/j.jneuroim.2025.578662","DOIUrl":"10.1016/j.jneuroim.2025.578662","url":null,"abstract":"<div><div>Common Variable Immunodeficiency (CVID) is a primary immunodeficiency disorder that often presents with recurrent infections and autoimmune complications, leading to diagnostic delays. This case report presents two adult male patients, ages 44 and 42, with prolonged histories of recurrent pneumonia, sinusitis, meningitis, and autoimmune encephalitis. Both cases were initially mismanaged due to the isolated treatment of symptoms, delaying the diagnosis of CVID. Comprehensive diagnostic evaluations eventually revealed low immunoglobulin levels, confirming the diagnosis. These cases highlight the importance of early recognition and a multidisciplinary approach to managing patients with recurrent infections and unusual presentations.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"406 ","pages":"Article 578662"},"PeriodicalIF":2.9,"publicationDate":"2025-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144253672","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":"Toll-like receptors 2 and 4 influence neuronal survival and glial reactions following ventral root crush injury in mice","authors":"Luciana Politti Cartarozzi ,&nbsp;Bruno Henrique de Melo Lima ,&nbsp;Ana Laura Rossi Midori Tomiyama ,&nbsp;Felipe Rabelo Santos ,&nbsp;Alexandre Leite Rodrigues de Oliveira","doi":"10.1016/j.jneuroim.2025.578655","DOIUrl":"10.1016/j.jneuroim.2025.578655","url":null,"abstract":"<div><div>Peripheral nerve injuries are followed by an increase in the expression of immune molecules, such as the major histocompatibility complex class I (MHC-I) and Toll-like receptors (TLR 2 and 4), which are mainly related to synaptic stability or elimination. The present study aimed to evaluate the putative role of TLR2 and 4 in neuronal survival, glial reaction and synaptic coverage after ventral root crush (VRC). To this end, 8-week-old male C57BL6/JUnib, TLR2 knockout, and TLR4 knockout strains were used. The animals underwent surgery for the crushing of L4, L5, and L6 ventral roots, and C57BL/6JUnib mice were further subdivided into control groups and groups of animals previously stimulated with TLR2 and TLR4 agonists (Pam3CSK4 and LPS, respectively; 1 h before surgery). Seven- and fourteen-days post-injury, spinal cords were collected for motoneuron survival analysis, immunohistochemistry (anti-Iba1, anti-GFAP, anti-synaptophysin), and synaptic coverage quantification. A subset of mice was also processed at 3 dpi for RT-qPCR and Western blotting. The results showed that TLR4 knockout mice exhibited greater susceptibility to motoneuron loss and decreased synaptic coverage after VRC, accompanied by increased NF-κB expression. In contrast, TLR2 knockout mice showed altered microglial responses, with reduced expression of Il10 and a distinct glial activation profile compared to wild-type mice and TLR4-deficient animals. Additionally, TLR2 stimulation with Pam3CSK4 led to a more intense microglial reaction surrounding motoneurons, along with increased Il10 gene expression, suggesting an anti-inflammatory phenotype. In the absence of TLR4, at 7 dpi, a reduction in amoeboid microglia was observed, which, coupled with the increased susceptibility of motoneurons and decreased synaptic coverage, reinforces the importance of immunomodulation in the early stages after injury. Together, these findings highlight distinct but complementary roles of TLR2 and TLR4 in shaping the neuroimmune response following VRC, with implications for understanding how innate immune signaling influences motoneuron survival and repair mechanisms.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"406 ","pages":"Article 578655"},"PeriodicalIF":2.9,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144253673","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":"Association of ADHD symptoms, pain, and tics with anti-thalamus antibodies in cerebrospinal fluid","authors":"Dominique Endres ,&nbsp;Katharina von Zedtwitz ,&nbsp;Alexander Rau ,&nbsp;Bernd Feige ,&nbsp;Hansjörg Mast ,&nbsp;Alexander Maier ,&nbsp;Marco Reisert ,&nbsp;Kathrin Nickel ,&nbsp;Joachim Brumberg ,&nbsp;Tobias Boettler ,&nbsp;Cornelia Glaser ,&nbsp;Nils Venhoff ,&nbsp;Horst Urbach ,&nbsp;Juan C. Baldermann ,&nbsp;Katharina Domschke ,&nbsp;Ludger Tebartz van Elst ,&nbsp;Luciana Hannibal ,&nbsp;Harald Prüss ,&nbsp;Simon J. Maier","doi":"10.1016/j.jneuroim.2025.578654","DOIUrl":"10.1016/j.jneuroim.2025.578654","url":null,"abstract":"<div><h3>Introduction</h3><div>Complex mixed presentations of severe mental disorders (SMD) with treatment resistance pose major challenges in clinical practice. The role of novel neuronal antibodies in cerebrospinal fluid (CSF) is largely unexamined in this context.</div></div><div><h3>Methods</h3><div>A well-studied paradigmatic case of a 36-year-old female patient is reported.</div></div><div><h3>Results</h3><div>She presented with attention-deficit/hyperactivity disorder-like symptoms (including frequent sensory overload), severe pain (pre-diagnosed as fibromyalgia and somatoform pain disorder), and motor tics. In addition, she developed secondary depressive symptoms. Various psychopharmacological treatment attempts were unsuccessful or not tolerated. The diagnostic routine work-up with a wide range of blood tests, electroencephalography (EEG), routine magnetic resonance imaging (MRI), cerebrospinal fluid (CSF) analyses, and [¹⁸F]fluorodeoxyglucose positron emission tomography revealed no clear pathological findings. Tissue-based assays using CSF material found strong immunoglobulin G antibody staining specifically directed against a cell population in the thalamus. Neurotransmitter measurements detected low GABA, glutamate and serotonin concentrations as well as high dopamine levels in the CSF. Different MRI-based analyses indicated no neurostructural alterations in the thalamus; however, left mesiotemporal volume loss was identified. The independent component analysis of the EEG showed left temporal theta waves, partly resembling spike-wave-complexes. Immunotherapy using high-dose steroids resulted in a partial improvement with subjectively reduced stimulus overload, intermediate disappearance of pain, and fewer tics. The improvement could not be objectified psychometrically/neuropsychologically. The mesiotemporal volume loss was no longer present. There were no relevant changes in further research MRI measurements of the thalamus including arterial spin labeling, diffusion tensor imaging, and diffusion microstructure imaging from pre to post-immunotherapy.</div></div><div><h3>Discussion</h3><div>Novel antibodies against strategic brain structures, such as the thalamus, might be associated with some complex SMD. Further immunopsychiatric research in this direction holds promise for a better understanding of similar patients.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"406 ","pages":"Article 578654"},"PeriodicalIF":2.9,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144548706","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":"Tumefactive demyelination as the first presentation of MOG ab-associated disease","authors":"Lin-Jie Zhang ,&nbsp;Yuan Qi ,&nbsp;Cui-Yun Sun ,&nbsp;Li Yang ,&nbsp;Chun-Sheng Yang","doi":"10.1016/j.jneuroim.2025.578653","DOIUrl":"10.1016/j.jneuroim.2025.578653","url":null,"abstract":"<div><div>Tumefactive demyelination is a rare but clinically significant manifestation of myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), often posing diagnostic challenges due to its resemblance to neoplastic lesions. We report a case of a 45-year-old woman presenting with a 3-week history of limb weakness, slowed responsiveness, and aphasia. Neurological examination revealed confusion and sensory aphasia. Serum MOG antibody was positive at a titer of 1:320, while AQP4 and GFAP antibodies were negative. Cerebrospinal fluid (CSF) analysis showed a positive MOG antibody titer of 1:1. Brain MRI demonstrated a left frontal lobe mass with surrounding edema and patchy contrast enhancement. Brain biopsy revealed perivascular lymphocyte cuffing, focal myelin loss, and preserved axonal integrity, consistent with tumefactive demyelination. PET-CT revealed heterogeneous 11C-methionine (MET) and 18F-fluorodeoxyglucose (FDG) uptake, with an L/W_MET of 3.1 and L/W_FDG of 2.6, supporting a possible demyelinating process. The patient was diagnosed with MOGAD and treated with intravenous methylprednisolone (IVMP), resulting in complete symptom remission and significant lesion reduction on follow-up MRI. Tocilizumab was initiated for relapse prevention, and serum MOG antibody titers decreased from 1:320 to 1:100 over nine months. This case highlights the importance of integrating clinical, radiological, and pathological findings to differentiate tumefactive demyelination from neoplastic lesions. Early diagnosis and treatment are crucial for favorable outcomes in MOGAD-associated tumefactive demyelination.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"406 ","pages":"Article 578653"},"PeriodicalIF":2.9,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144213027","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":"Reversal of profound cortical atrophy with immunotherapy in pediatric anti-NMDA receptor encephalitis","authors":"Andy Liu ,&nbsp;Maeve C. Lucas ,&nbsp;Lilia Kazerooni ,&nbsp;Mariam M. Yousuf ,&nbsp;Saba Jafarpour ,&nbsp;Jonathan D. Santoro","doi":"10.1016/j.jneuroim.2025.578649","DOIUrl":"10.1016/j.jneuroim.2025.578649","url":null,"abstract":"<div><div>Anti-NMDA receptor (NMDAr) encephalitis is an autoimmune condition marked by neuropsychiatric symptoms and NMDAr IgG autoantibodies in the serum and/or cerebrospinal fluid. While MRI findings are often nonspecific or normal, the reversibility of imaging abnormalities with immunotherapy remains underexplored. We report a 3-year-old girl who presented with seizures, altered mental status, and encephalopathy diagnosed with medically refractory anti-NMDAR encephalitis. Initial neuroimaging was unremarkable, but subsequent MRIs revealed T2 hyperintensities and leptomeningeal enhancement. After delayed treatment with IVIG, methylprednisolone, Rituximab, and plasmapheresis, the patient showed clinical improvement. Observational MRI scans after treatment demonstrated reduced parenchymal volume loss and stabilization of T2 changes over 4.5 years. This case highlights the potential for clinical and radiographic improvement after treatment in anti-NMDAR encephalitis and the benefit of immunomodulatory therapy even years after presentation.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"406 ","pages":"Article 578649"},"PeriodicalIF":2.9,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144169088","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":"An updated, comprehensive meta-analysis of the treatment of anti-NMDAR encephalitis: Analysis, equipoise, and the urgent need for evidence over anecdote","authors":"Yoji Hoshina ,&nbsp;Tammy L. Smith ,&nbsp;Alen Delic MSTAT ,&nbsp;Ka-Ho Wong ,&nbsp;Lisa K. Peterson ,&nbsp;Anastasia Zekeridou ,&nbsp;Albert Aboseif ,&nbsp;Christopher Coffey ,&nbsp;Melissa A. Wright ,&nbsp;Brenda Banwell ,&nbsp;Annalisa Dialino-Felix ,&nbsp;Susan Flavin ,&nbsp;Lisa Dill ,&nbsp;Maarten J. Titulaer ,&nbsp;Gregory S. Day ,&nbsp;Stacey L. Clardy","doi":"10.1016/j.jneuroim.2025.578651","DOIUrl":"10.1016/j.jneuroim.2025.578651","url":null,"abstract":"<div><h3>Background</h3><div>There are no FDA-approved treatments for anti-<em>N</em>-methyl-<span>d</span>-aspartate receptor encephalitis (NMDARE), and no prospective, multicenter clinical trials have been completed to provide evidence for management of this disease. We evaluated changes in treatment strategies and outcomes since the previous comprehensive review in 2019.</div></div><div><h3>Methods</h3><div>A systematic literature review was conducted in PubMed capturing manuscripts published from January 2019 through March 2024. Demographic and clinical data were extracted from articles containing individual immunotherapy data in NMDARE and were compared to a previously published literature review. Studies with ≥10 cases, ≥6 months follow-up, and outcomes reported as favorable (modified Rankin Scale [mRS] 0–2) and poor (mRS 3–5 or 3–6), were grouped and summarized by diagnosis period.</div></div><div><h3>Results</h3><div>Among 649 patients from 321 articles, first- (from 91.3 % to 98.3 %, <em>p</em> &lt; 0.001) and second-line (from 31.8 % to 42.5 %, p &lt; 0.001) immunotherapy use has increased. The proportion of patients receiving immunotherapy within 30 days of symptom onset increased from 50.1 % to 72.5 % (p &lt; 0.001). Favorable outcome (mRS 0–2) increased from 71.5 % to 76.7 % (<em>p</em> = 0.024), while mortality (6.3 % to 6.9 %, <em>p</em> = 0.714) and relapse rates (12.6 % vs. 13.2 %, <em>p</em> = 0.789) remained unchanged. Data from larger cohort studies of patients diagnosed with NMDARE after 2013 have reported wide variability in the proportion of patients achieving a favorable outcome at final follow-up, ranging from 56 % to 93 %, depending on the institution and follow-up duration.</div></div><div><h3>Conclusions</h3><div>Since 2019, more patients have been treated early with first- and second-line immunotherapies. Functional outcomes have shown modest improvements, whereas mortality and relapse rates have remained unchanged.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"405 ","pages":"Article 578651"},"PeriodicalIF":2.9,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144204600","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":"Inflammatory cerebral pseudotumour as a rare manifestation of neuro-Behçet's disease: A case report and literature review","authors":"Óscar Porto Fuentes ,&nbsp;Laura Lacruz Ballester ,&nbsp;Jorge Álvarez Troncoso ,&nbsp;Clara Itzíar Soto Abánades ,&nbsp;Ana Noblejas Mozo ,&nbsp;Ángel Robles Marhuenda ,&nbsp;Juan José Ríos Blanco ,&nbsp;Belén Gutiérrez Sancerni ,&nbsp;Isabel Esteban Rodríguez ,&nbsp;Elvira Tornay Mora ,&nbsp;Elena Martínez Robles","doi":"10.1016/j.jneuroim.2025.578652","DOIUrl":"10.1016/j.jneuroim.2025.578652","url":null,"abstract":"<div><div>Neurological involvement in Behçet's syndrome is rare but is associated with significant morbidity and mortality. Two subtypes of neuro-Behçet's disease (NBD) are typically described: parenchymal and non-parenchymal. Among parenchymal manifestations, some cases of inflammatory pseudotumoural lesions have been reported, occasionally requiring a brain biopsy to differentiate them from central nervous system (CNS) neoplasms or infections. We present a new case of cerebral pseudotumour in a patient without a prior diagnosis of Behçet's syndrome. We review the literature, highlighting the distinguishing features in comparison with typical parenchymal neuro-Behçet's disease.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"405 ","pages":"Article 578652"},"PeriodicalIF":2.9,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144167661","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":"Heightened effector immune cell infiltration of the hippocampus concurrently with brain ventricular volume expansion in aged APP/PS1 mice","authors":"Mark A. Maynes ,&nbsp;Carley A. Owens ,&nbsp;Delaney M. Anani-Wolf ,&nbsp;Zachariah P. Tritz ,&nbsp;Fang Jin ,&nbsp;Michael J. Hansen ,&nbsp;Marina Seady ,&nbsp;Aaron J. Johnson","doi":"10.1016/j.jneuroim.2025.578646","DOIUrl":"10.1016/j.jneuroim.2025.578646","url":null,"abstract":"<div><div>Alzheimer's disease (AD) is the most common form of dementia for which the role of neuroinflammation is becoming more realized. Recent studies have shown that immune cells infiltrate the hippocampus and the cortex of AD patients as well as mouse models of the disease. In this study, we employed T2-weighted magnetic resonance imaging (MRI) to view changes in ventricular volume in addition to spectral flow cytometric assessment of the hippocampus infiltrating immune profile in the aged APP/PS1 mice. Aged APP/PS1 mice present with increased size of lateral, dorsal, and ventral ventricles plus increased numbers of hippocampus infiltrating effector immune cell subsets, including CD8 T cells expressing IFNγ, granzyme B, and perforin along with other cell types such as γδ T cells, neutrophils, and NK cells. The concurrent increase in effector cell types with ventricular enlargement expands the putative mechanism of brain atrophy in the APP/PS1 mouse model to include cytolytic functions of these aforementioned immune cell subsets.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"406 ","pages":"Article 578646"},"PeriodicalIF":2.9,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144169019","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":"SPI1 affects Aβ1–42-induced microglia-mediated neuroinflammation by transcriptionally regulating FOSL2 expression","authors":"Jing Du ,&nbsp;ZeXin An","doi":"10.1016/j.jneuroim.2025.578650","DOIUrl":"10.1016/j.jneuroim.2025.578650","url":null,"abstract":"<div><h3>Background</h3><div>Microglia-induced-neuroinflammation contributes to Alzheimer's disease (AD) progression. SPI1 has been implicated in neuroinflammation and neuronal function and participated in AD progression. However, the underlying mechanism of SPI1 in microglia-induced neuroinflammation remains unclear.</div></div><div><h3>Methods</h3><div>The levels of inflammatory factors in cell supernatant were determined using ELISA. Cellular morphology was observed through an inverted microscope. Gene and protein expression levels were detected using western blot, RT-qPCR and IF assay. The interaction between SPI1 and FOSL2 promoter was verified using dual luciferase experiment and ChIP.</div></div><div><h3>Results</h3><div>A cell model of AD was successfully established, as evidenced by elevated inflammatory factors and altered cellular morphology. Besides, SPI1 and FOSL2 were elevated in BV2 cells by Aβ₁_–₄₂ induction. Furthermore, SPI1 knockdown or FOSL2 knockdown promoted M2 polarization in Aβ₁_–₄₂-induced BV-2 cells. Mechanistically, SPI1 bound to FOSL2 promoter to promote its transcriptional activity and expression of FOSL2. As expected, SPI1 knockdown facilitated M2 polarization in Aβ₁_–₄₂-induced BV-2 cells by inhibiting FOSL2 expression and inactivating JAK2/STAT3 pathway.</div></div><div><h3>Conclusion</h3><div>SPI1 knockdown promoted M2 polarization of microglia, thereby suppressing neuroinflammation through suppression of the FOSL2/JAK2/STAT3 pathway, ultimately alleviating AD progression.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"406 ","pages":"Article 578650"},"PeriodicalIF":2.9,"publicationDate":"2025-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144178818","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}