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Keywords {🔍}

cells, erap, pyroptosis, cell, caspase, pubmed, patients, article, expression, arthritis, google, scholar, fig, signaling, pathway, nlrp, activation, hedgehog, controls, significantly, cas, rheumatoid, levels, synovial, activated, tissue, study, shown, asc, central, data, human, protein, gli, found, gsdmdn, control, staining, analysis, inflammatory, cleaved, normal, death, release, immunol, ldh, flow, representative, inflammation, ilβ,

Topics {✒️}

n-terminal pore-forming domain myeloid foxo1-beta-catenin axis β-catenin-mediated activity mir-125a-3p/gsdmd axis [13] mir-125a-3p/gsdmd axis 25μl/ml human cd3/cd28 hedgehog/smo/gli1 signaling axis nod/shiltjgpt-prkdcem26cd52il2rgem26cd22/gpt nc sds-page gels bio-rad image system nod/shiltjgpt-prkdcem26cd52il2rgem26cd22/gpt rna-quick purification kit anti-cd3/cd28 beads nucleotide-binding oligomerization segment additional information publisher erap2/hedgehog signaling axis erap2-hedgehog signaling axis edta-k2 anticoagulation tubes hedgehog/smo/gli1 pathway shh-gli signaling pathway cd47-sirpα activates privacy choices/manage cookies controls nek7/nlrp3 activity research involving animal quantitative rt-pcr hedgehog signaling pathway rheumatism collaborative initiative secreted il-1β measured pyroptosis/caspase-1 assay kit annexin v-pe bmc hedgehog/gli1 signaling authors scientific editing anti-beta-actin hedgehog signal pathway lv-nc/ lv-erap2 classical signaling pathway de boer jh synovial fibroblast proliferation pro-inflammatory cytokines state privacy rights triggers immune responses anti-human cd3 springer nature humanized mouse model caspase-1 detection kit measuring ldh release hedgehog pathway activator anti-inflammatory genes fluorescently labeled cells

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         headline:Endoplasmic reticulum aminopeptidase 2 regulates CD4+ T cells pyroptosis in rheumatoid arthritis
         description:Rheumatoid arthritis (RA) is a chronic, progressive autoimmune disease with a complex pathogenesis that has not yet been fully elucidated, and T-cell pyroptosis is an important pathogenetic factor in RA. This study aimed to investigate the role of endoplasmic reticulum aminopeptidase 2 (ERAP2) in the pyroptosis of CD4+ T cells in RA and the specific molecular mechanism. Peripheral venous blood was collected from human subjects, and CD4+ T cells were isolated and activated to measure the level of pyroptosis and ERAP2 expression. Pyroptosis levels were assessed using immunofluorescence, flow cytometry, qRT-PCR, and Western blotting. Changes in pyroptosis levels were observed upon knockdown or overexpression of ERAP2. To detect activated Caspase-1 in tissues, chimeric mice were engrafted with human synovial tissue and reconstituted with human CD4+ T cells. CD4 + T cells were treated with GLI1 antagonists and SMO receptor agonists to detect changes in pyroptosis levels. CD4+ T cell levels undergoing pyroptosis were found to be elevated in the blood and synovium of RA patients. The gene and protein expression of ERAP2 were significantly higher in CD4+ T cells from RA patients. Deletion of ERAP2 suppressed pyroptosis of these cells, attenuated the activation of Caspase-1 in tissue T cells, and reduced tissue inflammatory responses. Reciprocally, overexpression of ERAP2 triggered inflammasome assembly, activated Caspase-1, and induced pyroptosis in CD4+ T cells. Mechanistically, ERAP2 inhibits the Hedgehog signaling pathway and upregulates the expression of nucleotide-binding oligomerization segment-like receptor family 3(NLRP3), cleaved Caspase-1, and Gasdermin D to promote pyroptosis in CD4+ T cells. Taken together, our results identify a novel mechanism by which ERAP2 regulates RA development and document the effect of the ERAP2/Hedgehog signaling axis on pyroptosis of CD4+ T cells from RA patients.
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      headline:Endoplasmic reticulum aminopeptidase 2 regulates CD4+ T cells pyroptosis in rheumatoid arthritis
      description:Rheumatoid arthritis (RA) is a chronic, progressive autoimmune disease with a complex pathogenesis that has not yet been fully elucidated, and T-cell pyroptosis is an important pathogenetic factor in RA. This study aimed to investigate the role of endoplasmic reticulum aminopeptidase 2 (ERAP2) in the pyroptosis of CD4+ T cells in RA and the specific molecular mechanism. Peripheral venous blood was collected from human subjects, and CD4+ T cells were isolated and activated to measure the level of pyroptosis and ERAP2 expression. Pyroptosis levels were assessed using immunofluorescence, flow cytometry, qRT-PCR, and Western blotting. Changes in pyroptosis levels were observed upon knockdown or overexpression of ERAP2. To detect activated Caspase-1 in tissues, chimeric mice were engrafted with human synovial tissue and reconstituted with human CD4+ T cells. CD4 + T cells were treated with GLI1 antagonists and SMO receptor agonists to detect changes in pyroptosis levels. CD4+ T cell levels undergoing pyroptosis were found to be elevated in the blood and synovium of RA patients. The gene and protein expression of ERAP2 were significantly higher in CD4+ T cells from RA patients. Deletion of ERAP2 suppressed pyroptosis of these cells, attenuated the activation of Caspase-1 in tissue T cells, and reduced tissue inflammatory responses. Reciprocally, overexpression of ERAP2 triggered inflammasome assembly, activated Caspase-1, and induced pyroptosis in CD4+ T cells. Mechanistically, ERAP2 inhibits the Hedgehog signaling pathway and upregulates the expression of nucleotide-binding oligomerization segment-like receptor family 3(NLRP3), cleaved Caspase-1, and Gasdermin D to promote pyroptosis in CD4+ T cells. Taken together, our results identify a novel mechanism by which ERAP2 regulates RA development and document the effect of the ERAP2/Hedgehog signaling axis on pyroptosis of CD4+ T cells from RA patients.
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         CD4+ T cells
         ERAP2
         Rheumatoid arthritis
         Hedgehog signaling pathway
         Rheumatology
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