SLP65 _ BLNK
- Known as:
- SLP65 _ BLNK
- Catalog number:
- 11-411-C100
- Product Quantity:
- 0.1 mg
- Category:
- -
- Supplier:
- Exbio
- Gene target:
- SLP65 _ BLNK
Related genes to: SLP65 _ BLNK
- Gene:
- BLNK NIH gene
- Name:
- B cell linker
- Previous symbol:
- -
- Synonyms:
- SLP65, Ly57, SLP-65, BLNK-s, BASH, bca
- Chromosome:
- 10q24.1
- Locus Type:
- gene with protein product
- Date approved:
- 2001-07-16
- Date modifiied:
- 2019-04-23
Related products to: SLP65 _ BLNK
Related articles to: SLP65 _ BLNK
- BackgroundMicroglia play a central role in Alzheimer's disease (AD) pathogenesis, yet it remains unclear whether microglia-related gene expression changes contribute causally to disease risk or reflect downstream responses to neurodegeneration.ObjectiveThis study aimed to systematically identify microglia-expressed genes with genetically regulated expression associated with AD risk and to characterize their functional relevance through integrative genomic analyses.MethodsWe compiled 2454 microglia-associated genes from four transcriptomic studies and five expression databases. Using brain cis-eQTL data from PsychENCODE (n = 1387), we performed summary-data-based Mendelian randomization (SMR) and HEIDI tests with AD GWAS data (111,326 cases, 677,663 controls). Significant SMR signals (FDR < 0.05) were evaluated using Bayesian colocalization. Regulatory context was assessed via overlap with PU.1-associated chromatin features, and differential expression was examined using single-nucleus RNA-seq from AD brains.ResultsSMR identified 16 genes whose genetically predicted expression was associated with AD risk (FDR < 0.05), including (OR = 1.10, 95% CI: 1.07-1.13) and (OR = 0.90, 0.86-0.95). Colocalization supported shared causal variants at eight loci (PPH4 > 0.8; e.g., , , ). Most prioritized genes overlapped with PU.1-associated regulatory regions. Single-nucleus RNA-seq confirmed dysregulation of several candidates (e.g., , ) in AD microglia.ConclusionsWe identify microglia-expressed genes with genetic evidence consistent with a potential causal role in AD. These genes are enriched in microglia-specific regulatory elements and exhibit transcriptional alterations in AD, highlighting microglial pathways as potential therapeutic targets. - Source: PubMed
Publication date: 2026/06/02
Zhao YuanyuanLiu ConghuiYv KekeWang NanLi Zuowei - Autoimmune nodopathies (AINs) are rare acquired autoimmune neuropathies with distinct clinical features and circulating autoantibodies, often of the immunoglobulin G4 (IgG4) subclass, targeting proteins at the node of Ranvier. Defects in B cell tolerance checkpoints have been implicated in several autoimmune diseases, including MuSK-positive myasthenia gravis, another IgG4 autoantibody-mediated disease. Here, we investigated whether tolerance defects exist in neurofascin-155-mediated AIN (NF155-AIN), using a well-established assay, by generating recombinant antibodies from new emigrant (NE) and mature naive (MN) B cells from three NF155-AIN patients, and tested them for polyreactivity and autoreactivity. Additionally, we analyzed the transcriptome of peripheral blood mononuclear cells, with a particular focus on naive B cells and CD4+ T cells at the single-cell level, and characterized cell-cell interactions. NF155-AIN patients have an elevated frequency of polyreactive B cells in the NE (37.4% compared to 9.7% in healthy controls (HCs), = 0.03) and MN (31.5% compared to 10.5% in HCs, = 0.03) compartments, consistent with a breach in early B cell tolerance checkpoints. In this unbiased exploratory transcriptomics analysis, we observed potentially abnormal B cell receptor (BCR) signaling characterized by low CD79B, CSK, BLNK, and BTK expression, and possible impaired CD4+ T cell regulatory function. Moreover, comparison with chronic inflammatory demyelinating polyneuropathy, a related autoimmune neuropathy, suggested that these differences are specific to NF155-AIN. A breach in early B cell tolerance checkpoints, with defective BCR signaling, and disrupted T cell-B cell interactions in NF155-AIN, may contribute to the development of pathogenic autoreactivity. - Source: PubMed
Publication date: 2026/04/20
Roy BhaskarObaid Abeer HWang ZhenjianKovacs Kristof GOhashi SarahKalayci F Naz CemreJoo DanielMasi GianvitoCoppola CarminaDas SameeranHernandez Amanda LMartin-Aguilar LorenaLleixà CintaNowak Richard JQuerol LuisO'Connor Kevin C - BACKGROUND: Brain-resident microglia and infiltrating monocyte-derived macrophages are among the main effectors in regulating innate immunity and mediating neuroinflammation after traumatic brain injury (TBI). Our previous work demonstrated that circulating extracellular vesicles from TBI patients (TEVs) aggravate microglial/macrophage activation and associated neuroinflammatory damage. However, the key molecular regulators governing TBI-induced and TEV-aggravated microglial/macrophage responses remain elusive. METHODS: To identify key molecular regulators of microglial/macrophage activation during the acute phase after TBI, we first performed RNA-sequencing on mouse TBI brains at multiple acute time points, and on brains from TBI mice treated with TEVs. We then integrated and analyzed a public single-nucleus RNA-sequencing dataset from human TBI brains (GSE209552) to validate and extend our murine findings. After hub gene identification, we used complementary in vivo (TBI and TBI + TEV mice) and in vitro [oxygen-glucose deprivation/re-oxygenation (OGD/R)-stimulated and TEV-stimulated BV2 cells] models for mechanistic investigation. RESULTS: Multi-dimensional bioinformatics analyses identified six hub genes, including HCK, BLNK, C1QB, CTSC, P2RY6, and VAV1, consistently implicated in microglial/macrophage activation throughout the acute phase after TBI. Subsequent mechanistic investigations focused on hematopoietic cell kinase (HCK), a central node within this hub gene network. Pharmacological inhibition of HCK kinase activity with A-419259 was found to (1) alleviate TBI-induced and TEV-aggravated microglial/macrophage activation and recruitment, (2) promote a phenotypic shift from pro-inflammatory M1 toward anti-inflammatory/reparative M2 polarization, and (3) suppress the activation of microglial/macrophage nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3) inflammasome. These effects collectively ameliorated secondary brain damage and improved neurological outcomes after TBI. Complementary in vitro studies confirmed that A-419,259 treatment alleviated OGD/R-stimulated or TEV-stimulated BV2 microglial activation and NLRP3 inflammasome activation, while facilitating the M1-to-M2 transition. CONCLUSIONS: Our findings identify HCK as a pivotal molecular regulator of microglia/macrophage-mediated neuroinflammation, thus providing a potential therapeutic target for ameliorating secondary brain injury after TBI. - Source: PubMed
Publication date: 2026/04/09
Li LeiLu TaoyuanGao WeiweiLi FanjianGuo XinGuan SiyuGheyret DilmuratWang JinchaoLi TuoCao YiyaoHuang ChuanJiang RongcaiZhang ShuLiu DianweiZhang JianningXu Xin - Chronic lung allograft dysfunction (CLAD) leads to declining respiratory function and high mortality, representing the main barrier to long-term survival in lung transplantation (LT). We performed the first genome-wide association study (GWAS) investigating donor's and recipient's genetic factors associated with CLAD. - Source: PubMed
Publication date: 2026/03/19
Brocard SimonMauduit VincentMorin MartinBoussamet LéoSilva Nayane Dos Santos BritoDurand AxelleHalitim PierreRenaud-Picard BenjaminCoiffard BenjaminDemant XavierFalque LoïcLe Pavec JéromeRoux AntoineVilleneuve ThomasKnoop ChristianeMerveilleux ClaireSalpin MathildeCarlier NicolasGourraud Pierre AntoineMagnan AntoineLair DavidBerthelot LaurelineSüdholt MarioVince NicolasTissot AdrienLimou Sophie - Accumulating evidence indicates that Alzheimer disease (AD) is caused by dysregulated microglial phagocytosis. The main risk factor for AD is age, and ageing reduces microglial phagocytosis of amyloid-β (Aβ) plaques, while increasing microglial phagocytosis of synapses and neurons. Most of the known genetic risk for AD can be linked to microglial phagocytosis, including ABCA1, ABI3, ACE, ADAM17, APOE, APP, BIN1, BLNK, CD2AP, CD33, CLU, CR1, CTSB, CTSH, EED, GRN, INPP5D, LILRB2, PICALM, PLCG2, PSEN1, PTK2B, SIGLEC11, SORL1, SPI1, TMEM106B and TREM2. Moreover, the only disease-modifying treatments for AD - anti-Aβ antibodies - work by increasing microglial phagocytosis of Aβ aggregates. Microglial phagocytosis of Aβ via TREM2, LRP1, CD33, TAM receptors and anti-Aβ antibodies appears to reduce AD pathology by pruning and compacting plaques, restricting subsequent tau pathology, whereas microglial phagocytosis of synapses and neurons seems detrimental in the later stages of AD, via complement, P2Y receptor and TREM2. However, the roles of microglial phagocytosis in AD are complex and multifaceted, and improved treatments are likely to require a deeper understanding of these roles. - Source: PubMed
Publication date: 2025/11/28
Brown Guy CSt George-Hyslop PeterPaolicelli Rosa CLemke Greg