Journal of Neuroinflammation最新文献

{"title":"FPR2 deficiency alleviates LPS-induced depressive-like behaviors in mice by suppressing the microglial CSF1/NLRP3 inflammasome pathway.","authors":"Hanqi Wang, Yijun Chen, Junna Chang, Zhen Liu, Yang Yu","doi":"10.1186/s12974-026-03963-4","DOIUrl":"10.1186/s12974-026-03963-4","url":null,"abstract":"<p><p>Depression is one of the most prevalent psychiatric disorders worldwide, yet its pathogenesis remains unclear. Here, we aimed to investigate the effects of formyl peptide receptor 2 (FPR2), a key regulator of innate immunity and inflammation, on lipopolysaccharide (LPS)-induced depression-related behaviors in mice after intraperitoneal administration, and to elucidate its regulatory mechanisms in microglia. FPR2 knockout (Fpr2^-/-) significantly attenuated LPS-induced depressive and anxiety-like behaviors in mice. LPS markedly increased FPR2 expression in microglia of the prefrontal cortex (PFC) and hippocampus, while only a minimal increase was observed in neurons. FPR2 deficiency alleviated LPS-induced microglial activation and reduced neuronal synaptic alterations. RNA sequencing and validation experiments confirmed that FPR2 deletion substantially decreased LPS-induced microglial NLRP3 inflammasome activation and IL-1β levels in the brain. Mechanistically, FPR2 regulated downstream NLRP3 activation by modulating CSF1, and FPR2/CSF1 activation was governed by its upstream ligand, serum amyloid A (SAA). Analysis of public clinical datasets revealed that SAA1 levels were significantly upregulated in the orbital ventral PFC of patients with major depressive disorder (MDD) and in the plasma of patients with late-life depression. These findings demonstrate that the SAA/FPR2/CSF1/NLRP3 pathway mediates LPS-induced depressive-like behaviors by regulating microglial activation and neuroinflammation.</p>","PeriodicalId":16577,"journal":{"name":"Journal of Neuroinflammation","volume":" ","pages":""},"PeriodicalIF":11.5,"publicationDate":"2026-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13656527/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148455951","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Circulating immune profiling reveals impaired monocyte states and trajectories driving immunosuppression in glioblastoma.","authors":"Andrea Scafidi, Tony Kaoma, Claudia Cerella, Eleonora Campus, Kamil Grzyb, Bakhtiyor Nosirov, Frida Lind-Holm Mogensen, Eliane Klein, Raul Da Costa, Alexander Skupin, Frank Hertel, Guy Berchem, Michel Mittelbronn, Antonio Cosma, Beatrice Melin, Simone P Niclou, Petr V Nazarov, Anna Golebiewska, Aurélie Poli, Alessandro Michelucci","doi":"10.1186/s12974-026-03964-3","DOIUrl":"10.1186/s12974-026-03964-3","url":null,"abstract":"<p><strong>Background: </strong>Glioblastoma (GBM) is an aggressive and lethal brain tumor marked by profound local and systemic immune dysfunction. Despite evidence of peripheral immune impairment, the clinical relevance of these alterations for diagnostic or therapeutic purposes remains poorly defined.</p><p><strong>Methods: </strong>We performed multimodal single-cell profiling of peripheral blood mononuclear cells from a single-center cohort of treatment-naïve GBM patients and healthy donors, integrating mass and flow cytometry with single-cell RNA-sequencing. Unsupervised clustering, pseudo-temporal trajectory analyses and cell-cell communication inference were applied to map immune states and their interactions.</p><p><strong>Results: </strong>GBM blood profiles were characterized by heterogeneous changes in classical monocytes, encompassing expanded, reduced and unchanged subsets with distinct functional states, including antigen-presenting, interferon and metabolic programs. Additional myeloid adaptations included myeloid-derived suppressor cell (MDSC) expansion and loss of non-classical monocytes. Trajectory analyses identified a differentiation continuum, evolving from antigen-presenting to metabolic monocyte subsets, and positioning MDSCs as an intermediate state. Antigen‑presenting monocytes displayed tumor‑migratory, precursor‑like profiles that corresponded to tumor‑associated macrophages in public GBM datasets. Across subsets, circulating monocytes shared a \"GBM-classical monocytic signature\" characterized by low MHC class II expression, altered cell-cell communication and upregulation of anti-inflammatory mediators, including IL1R2 and CD163. Notably, complementary myeloid expression signatures were identified across patients, indicating distinct systemic immune phenotypes. In parallel, lymphocyte alterations included decreased proportions of CD4⁺ T, natural killer (NK) and CD56⁺ T cells, retaining relatively conserved activation profiles, exemplified by up-regulation of alarmins S100A8/S100A9.</p><p><strong>Conclusions: </strong>These findings delineate systemic immune reprogramming in primary GBM, characterized by coordinated myeloid and lymphocyte alterations. The identification of circulating monocyte states with transcriptional continuity to the tumour microenvironment, alongside distinct patient-level systemic myeloid signatures, provides a framework for exploring peripheral blood as a source of immune biomarkers in GBM.</p>","PeriodicalId":16577,"journal":{"name":"Journal of Neuroinflammation","volume":" ","pages":""},"PeriodicalIF":11.5,"publicationDate":"2026-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13555986/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148471400","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ferritin-ApoE nanocarrier for targeted therapy of neuromyelitis optica spectrum disorder in mice.","authors":"Xin Zhao, Qian Liang, Kangqi Lin, Shihe Jiang, Tian Yang, Mengjiao Sun, Run Song, Junqiang Yan, Sara Palma-Tortosa, Zaal Kokaia, Xiyun Yan, Ganqin Du, Kelong Fan, Wei-Na Jin","doi":"10.1186/s12974-026-03935-8","DOIUrl":"10.1186/s12974-026-03935-8","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Neuromyelitis optica spectrum disorder (NMOSD) is a chronic inflammatory autoimmune disease affecting the central nervous system (CNS), characterized by anti-aquaporin 4 (AQP4) antibody-mediated damage to astrocytes, resulting in subsequent demyelination. Our prior work identified the protective effects of the apolipoprotein E&lt;sub&gt;130-149&lt;/sub&gt; (ApoE&lt;sub&gt;130-149&lt;/sub&gt;) peptide in NMOSD mice by promoting astrocyte-microglia intercellular communication. However, its therapeutic potential is restricted due to the limited penetration of the blood-brain barrier (BBB) with systemic administration. Here, we designed a heavy-chain ferritin (HFn)-based nanocarrier containing the ApoE&lt;sub&gt;130-149&lt;/sub&gt; peptide (HFn-ApoE&lt;sub&gt;130-149&lt;/sub&gt;), specifically engineered for CNS delivery.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;HFn-ApoE&lt;sub&gt;130-149&lt;/sub&gt; was constructed through genetic engineering by fusing the coding sequence of HFn with that of the ApoE&lt;sub&gt;130-149&lt;/sub&gt; peptide in a recombinant plasmid. An acute NMOSD mouse model was induced by transcranial co-injection of AQP4-IgG and human complement (hC) into the brain. The distribution of Cy5.5-labeled HFn-ApoE&lt;sub&gt;130-149&lt;/sub&gt; post intravenous injection was tracked using in vivo fluorescence imaging to confirm its presence in the brain and peripheral organs. Lesions in the brain were quantified using T2-weighted 7 Tesla magnetic resonance imaging (7T-MRI). Neuropathological features of NMOSD were evaluated by immunostaining of brain sections. Neuroinflammation and immune cell infiltration were analyzed via flow cytometry. The key signaling pathways regulated by HFn-ApoE&lt;sub&gt;130-149&lt;/sub&gt; were investigated through Western blot (WB) analysis. The interaction between HFn-ApoE&lt;sub&gt;130-149&lt;/sub&gt; and its receptors was validated through co-immunoprecipitation and visualized on microglia using proximity ligation assay (PLA). Finally, the therapeutic effect on spatial learning and memory was evaluated using the Morris water maze (MWM) test.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;The HFn-ApoE&lt;sub&gt;130-149&lt;/sub&gt; effectively crossed the BBB, attenuated lesion progression and demyelination, as well as preserved AQP4 expression and astrocytic integrity in NMOSD mice. The treatment induced a spatial and phenotypic restructuring of the astrocytic response, notably reducing excessive astrocyte accumulation around lesions while encouraging a proliferative and reparative phenotype. Furthermore, HFn-ApoE&lt;sub&gt;130-149&lt;/sub&gt; influenced microglial polarization towards an anti-inflammatory state, reducing infiltration of peripheral immune cells. Mechanistically, HFn-ApoE&lt;sub&gt;130-149&lt;/sub&gt; exerted its anti-inflammatory effects through the low-density lipoprotein receptor-related protein 1 (LRP1) -nuclear factor kappa B (NF-κB) signaling axis in microglia. Functional binding of HFn-ApoE&lt;sub&gt;130-149&lt;/sub&gt; to LRP1 suppressed inhibitor of NF-κB (IκBα) phosphorylation, thereby inhibiting NF-κB nuclear translocation and ","PeriodicalId":16577,"journal":{"name":"Journal of Neuroinflammation","volume":" ","pages":""},"PeriodicalIF":11.5,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13647798/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148447526","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unknotting the nexus of asthma and neuroinflammation: from brain network alterations to therapeutic implications.","authors":"Wenjie Hu, Yanan Zou, Junbo Yin, Lei Liu, Yujie Ding, Xingzhe Gao, Yan Li, Xiangyi Kong","doi":"10.1186/s12974-026-03955-4","DOIUrl":"10.1186/s12974-026-03955-4","url":null,"abstract":"<p><p>Asthma is increasingly recognized as a systemic inflammatory syndrome that extends beyond the respiratory tract, with emerging evidence highlighting its relevance to neuroinflammation. The lung-brain axis-via interconnected inflammatory, vascular, metabolic, neural, and microbial pathways-provides a framework for understanding how chronic pulmonary disease may sustain or exacerbate neuroinflammatory processes. Mechanistically, asthma promotes blood-brain barrier disruption, systemic inflammation that seeds central neuroinflammation, oxidative stress, mitochondrial dysfunction, gut-lung-brain microbial crosstalk, and sleep fragmentation, all of which are biologically plausible drivers of sustained neuroinflammatory states and consequent neurodegenerative vulnerability. Epidemiological studies link asthma to increased risks of all-cause dementia and Alzheimer's disease, though cohort findings vary. Neuroimaging and biomarker evidence further support neuroinflammatory involvement, revealing altered hippocampal metabolism, white matter abnormalities, elevated plasma glial fibrillary acidic protein and neurofilament light chains, and cerebrospinal fluid markers of synaptic injury in severe or poorly controlled asthma-each reflecting neuroinflammatory or neurodegenerative sequelae. Links with Parkinson's disease and other neurodegenerative disorders remain more preliminary. Notably, asthma severity, phenotype, exacerbation frequency, and corticosteroid burden modulate neurological risk, suggesting that optimal disease control-potentially enhanced by biologic therapies-may confer neuroprotective benefits by dampening neuroinflammation. In conclusion, asthma should not be viewed solely as an airway disorder but as a potentially modifiable contributor to long-term brain vulnerability via neuroinflammatory pathways within the lung-brain axis. Future longitudinal studies integrating detailed phenotyping, biomarkers, and neuroimaging are needed to establish causality and guide anti-neuroinflammatory therapeutic strategies.</p>","PeriodicalId":16577,"journal":{"name":"Journal of Neuroinflammation","volume":" ","pages":""},"PeriodicalIF":11.5,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13647628/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148447548","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuroimmune braking mechanisms in exercise-related musculoskeletal injury: from nociceptors to tissue regeneration.","authors":"Enli Xie, Yushan He, Tainan Cao, Changchun Li, Zhiming Wang","doi":"10.1186/s12974-026-03938-5","DOIUrl":"10.1186/s12974-026-03938-5","url":null,"abstract":"<p><strong>Background: </strong>Musculoskeletal injuries are a frequent occurrence in sports medicine and rehabilitation, and their healing process needs an accurate response from inflammation. Recent studies show that sensory neurons play a critical role in tissue repair through neuropeptides, which is quite different from their usual function as simple pain detectors. The current review summarizes studies conducted during the last ten years concerning neuroimmune crosstalk mechanisms in musculoskeletal injury healing, in which the role of sensory neurons in macrophage polarization is emphasized.</p><p><strong>Methods: </strong>We reviewed preclinical studies on the neuro-immune interaction after musculoskeletal injury, emphasizing the CGRP-RAMP1-thrombospondin-1 axis and parallel pathways including TGF-β-mediated macrophage specification and TAFA4-IL-10 signaling. Based on rodent data regarding skin wounds, muscle injury, peripheral nerve injury, and other pertinent models, a theoretical model relating mechanical loading and neuroimmune inhibition was established.</p><p><strong>Results: </strong>CGRP-RAMP1-Thrombospondin 1 signaling pathway has been identified in preclinical studies as an candidate pathway for shifting macrophages from a pro-inflammatory (M1) to a pro-repair (M2) phenotype, hence balancing the process of pathogen clearance against tissue repair process. Parallel systems, such as TGF-β-mediated macrophage specification and TAFA4-IL-10 signaling, provide redundancy and robustness. Controlled loading, as seen with active recovery, causes stimulation of sensory neuron terminals, leads to the release of neuropeptides, triggers the neuroimmune braking process, and promotes proper M1-to-M2 conversion. The understanding of these mechanisms explains why patients have always been advised to undertake active recovery rather than rest following tendon/ligament damage.</p><p><strong>Conclusion: </strong>This review proposes a new conceptual framework in which the neuroimmune axis may serve as a key controller of musculoskeletal repair. These biological mechanisms offer a potential explanation for the medical choice of active recovery over complete rest following specific injuries; nevertheless, there is no direct evidence in humans, and this theory needs to be tested in human studies.</p>","PeriodicalId":16577,"journal":{"name":"Journal of Neuroinflammation","volume":" ","pages":""},"PeriodicalIF":11.5,"publicationDate":"2026-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13685355/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148436864","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Microglial mitophagy as an immunometabolic checkpoint in alzheimer's disease: linking mitochondrial quality control to neuroinflammation.","authors":"Mingyue Zou, Tengyu Zhao, Weidong Wu, Jian Zhang, Pengyu Pan, Jingdong Yan, Quan Li, Yanyan Zhou","doi":"10.1186/s12974-026-03946-5","DOIUrl":"10.1186/s12974-026-03946-5","url":null,"abstract":"<p><p>AD is a complex neurodegenerative disorder characterized by chronic neuroinflammation. Microglia, the brain's resident immune cells, centrally regulate AD pathophysiology. Recent studies have highlighted microglial mitophagy as an important interface linking mitochondrial quality control to innate immune responses.Intact mitophagy facilitates the timely clearance of damaged mitochondria, thereby limiting the release of mitochondrial DAMPs (e.g., mtDNA and mtROS) and helping restrain aberrant activation of the cGAS-STING pathway and the NLRP3 inflammasome.In the AD pathological milieu, however, factors including Aβ deposition, tau pathology, and genetic risk variants such as TREM2 and APOE4 disrupt mitophagy at multiple levels-from initiation and recognition to lysosomal degradation. This review systematically summarizes the molecular regulatory network of microglial mitophagy, with a particular focus on the mechanisms by which AD-associated pathological factors impair this process. We further discuss potential mechanisms through which mitophagic dysfunction may contribute to the amplification of neuroinflammation, including the release of mitochondrial DAMPs, the reprogramming of TBK1 signaling, and intercellular interactions. Finally, we outline current therapeutic strategies aimed at restoring mitophagy and discuss their potential to modulate neuroinflammatory responses and AD-related pathological processes, while highlighting the challenges and future directions in this emerging field.</p>","PeriodicalId":16577,"journal":{"name":"Journal of Neuroinflammation","volume":" ","pages":""},"PeriodicalIF":11.5,"publicationDate":"2026-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13545803/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148436831","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tertiary lymphoid structures in neuroinflammation coordinate neuroimmune homeostasis and pathological progression.","authors":"Yan Zhang, Peishen Han, Xiaoling Zhang","doi":"10.1186/s12974-026-03961-6","DOIUrl":"10.1186/s12974-026-03961-6","url":null,"abstract":"<p><p>The central nervous system (CNS) has long been considered immune privilege due to the blood-brain barrier, lack of traditional lymphatic drainage, and unique immune microenvironment. However, recent neuroimmunology research has demonstrated that the CNS maintains continuous communication with the peripheral immune system via meningeal lymphatic vessels, lymphoid systems, and border-associated macrophages. This paradigm shift has brought tertiary lymphoid structures (TLSs), ectopic lymphoid aggregates induced by chronic inflammation, infection, or tumors, into focus as key players in neuroimmune interactions. TLSs exert a dual effect in neuroinflammation. In infectious diseases like viral encephalitis, they promote local antibody production and T cell responses, aiding pathogen clearance. In contrast, in multiple sclerosis, autoimmune encephalitis, Alzheimer's disease, and Parkinson's disease, TLSs may sustain chronic inflammation, drive autoantibody production, and accelerate neurodegeneration. This review systematically summarizes the composition, induction mechanisms, and functional heterogeneity of TLSs across neurological diseases. We discuss their protective versus pathogenic roles in neuroinflammation and highlight their diagnostic value and therapeutic potential, aiming to provide new insights for precision intervention in neuroimmunological disorders.</p>","PeriodicalId":16577,"journal":{"name":"Journal of Neuroinflammation","volume":" ","pages":""},"PeriodicalIF":11.5,"publicationDate":"2026-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13640240/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148421889","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phosphorylated TYK2 orchestrates the pathogenic program of CD4 + T cells in the development of CNS autoimmunity.","authors":"Hao Wu, Zhiqiang Xiao, Zhiqing Mai, Guanyu Chen, Xiaoshuang Luo, Zuoyi Li, Minzhen Wang, Xiaoqing Chen, Zhuang Li, Dan Liang","doi":"10.1186/s12974-026-03934-9","DOIUrl":"10.1186/s12974-026-03934-9","url":null,"abstract":"<p><strong>Background: </strong>The imbalance between pathogenic Th1/Th17 cells and regulatory T cells (Tregs) is a central mechanism in central nervous system (CNS) autoimmune diseases, including autoimmune uveitis (AU) and multiple sclerosis. Tyrosine kinase 2 (TYK2) mediates signaling downstream of multiple cytokines implicated in CD4 + T cell differentiation, yet its subset-specific activation and therapeutic potential in CNS autoimmunity remain unclear. Here, we investigated the subset-specific activation of TYK2 and evaluated the therapeutic potential of selective TYK2 inhibition in CNS autoimmune diseases.</p><p><strong>Methods: </strong>TYK2 phosphorylation was examined in CD4 + T cell subsets from AU patients and from experimental autoimmune uveitis (EAU) and encephalomyelitis (EAE) models. The therapeutic effects and mechanisms of a selective TYK2 inhibitor were assessed using flow cytometry, single-cell RNA sequencing, adoptive transfer, in vitro cellular assays, and ex vivo stimulation of patient peripheral blood mononuclear cells.</p><p><strong>Results: </strong>TYK2 phosphorylation was preferentially activated in Th1 and Th17 cells compared with Tregs in both patients and disease models. TYK2 inhibition significantly reduced clinical and histopathological scores in EAU and EAE, suppressing Th1/Th17 differentiation and production of IFN-γ and IL-17A, while Treg proportion and function remained intact. Mechanistically, IFN-α/β, IL-12, and IL-23-but not IL-2-induced TYK2 phosphorylation in CD4 + T cells. Accordingly, TYK2 blockade selectively inhibited STAT1/2/3/4 activation downstream of these cytokines without affecting IL-2-induced STAT5 phosphorylation in Tregs. These lineage-selective effects were confirmed in peripheral blood mononuclear cells from AU patients.</p><p><strong>Conclusion: </strong>TYK2 acts as a lineage-selective therapeutic target in CNS autoimmunity. Its inhibition suppresses pathogenic Th1/Th17 responses while preserving Treg proportion and function by targeting cytokine-specific signaling pathways, thereby rebalancing the effector-regulatory immune axis.</p>","PeriodicalId":16577,"journal":{"name":"Journal of Neuroinflammation","volume":" ","pages":""},"PeriodicalIF":11.5,"publicationDate":"2026-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13445803/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148421881","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neutrophil extracellular traps exacerbate blood-brain barrier disruption in neuromyelitis optica spectrum disorder.","authors":"Xue Ma, Yao Wang, Xin Chen, Zonghao Pan, Yi Li, Kaixi Ren, Daidi Zhao, Hongzeng Li, Jun Guo","doi":"10.1186/s12974-026-03959-0","DOIUrl":"10.1186/s12974-026-03959-0","url":null,"abstract":"<p><p>Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune inflammatory disease of the central nervous system (CNS) characterized by recurrent optic neuritis and myelitis. Blood-brain barrier (BBB) disruption is a key pathological feature of NMOSD, but the role of neutrophil extracellular traps (NETs) in this process remains poorly defined. Serum proteomic profiling in patients with acute NMOSD revealed enrichment of the NET formation pathway. Neutrophils from these patients showed an increased propensity for NETosis, accompanied by elevated myeloperoxidase-DNA complexes, neutrophil elastase-DNA complexes, and cell-free DNA in serum, as well as increased neutrophil elastase-DNA complex levels in cerebrospinal fluid. In a murine NMOSD model, neutrophil depletion, peptidylarginine deiminase 4 inhibition (Cl-amidine), and NET degradation (DNase I) each attenuated astrocyte loss, demyelination, neuroinflammation, and BBB disruption. In vitro, patient-derived NETs downregulated tight junction proteins in bEnd.3 endothelial cells through mechanisms associated with myeloperoxidase and neutrophil elastase, while c-Jun N-terminal kinase inhibition mitigated NET-induced endothelial barrier disruption. Together, these findings suggest that aberrant NETosis may contribute to BBB disruption in acute NMOSD and support further investigation of NET-associated pathways as potential therapeutic targets.</p>","PeriodicalId":16577,"journal":{"name":"Journal of Neuroinflammation","volume":" ","pages":""},"PeriodicalIF":11.5,"publicationDate":"2026-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13632213/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148411980","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CXCL13⁺ CD4⁺ T cells are associated with B-cell recruitment and lesion progression in cerebral cavernous malformations.","authors":"Shaozhi Zhao, Yingxi Yang, Ran Huo, Qiuxia Zhou, Hongyuan Xu, Yingfan Sun, Hui Wang, Yang Ni, Yuming Jiao, Jiguang Wang, Dan Liu, Yong Cao","doi":"10.1186/s12974-026-03950-9","DOIUrl":"10.1186/s12974-026-03950-9","url":null,"abstract":"<p><p>Cerebral cavernous malformations (CCMs) are neurovascular abnormalities associated with lifelong risks of intracranial hemorrhage (ICH), seizures, and neurologic deficits, affecting approximately 0.16%~0.8% of the general population. Although immune cell infiltration is well recognized as promoting CCM progression, the mechanisms underlying their recruitment into the lesion microenvironment remain poorly understood. In our study, we employed single-cell RNA sequencing (scRNA-seq) to identify a significant enrichment of a CD4⁺ T-cell subset producing CXCL13 and decipher the cellular crosstalk within CCMs. The CXCL13-producing CD4⁺ T cells exhibited enhanced interaction with CXCR5⁺ memory B cells, which showed upregulation of genes related to activation, persistence, and targeted migration. Immunohistochemical staining supported the spatial co-localization between CXCL13⁺ CD4⁺ T cells and CXCR5⁺ CD20⁺ B cells, as well as a positive association between their abundances, reinforcing this cellular crosstalk and suggesting a potential role for CXCL13 in shaping the inflammatory microenvironment and local adaptive immune responses. Clinically, elevated CXCL13 expression in CCM lesions was associated with a higher frequency of subacute ICH and B-cell infiltration in patients. Finally, in vivo experiments showed that administration of recombinant CXCL13 increased B-cell infiltration and Prussian blue staining-defined lesion bleeding, whereas blockade of CXCL13 attenuated CCM lesion development. Thus, our study identified a potentially pathogenic CXCL13⁺ CD4⁺ T-cell subset in CCMs, providing a rationale for targeting CXCL13 signaling in CCMs.</p>","PeriodicalId":16577,"journal":{"name":"Journal of Neuroinflammation","volume":" ","pages":""},"PeriodicalIF":11.5,"publicationDate":"2026-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13628974/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148411878","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}