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https://proteomecentral.proteomexchange.org/dataset/PXD072439
Summary of dataset
Status: new
Identifier: PXD072439
HostingRepository: iProX
Species: Homo sapiens
Title: Lactate-Mediated Cross-Talk between KRT15 and GPR68 drives Type 2 Immunity in ECRSwNP
Submitter: Hongjie Du
LabHead: Ming Xia
Description: Eosinophilic chronic rhinosinusitis with nasal polyps (ECRSwNP) is a refractory inflammatory disease driven by type 2 immunity, yet the mechanistic link between epithelial stress and immune activation remains elusive. Here, we identify a pathogenic expansion of KRT5⁺KRT15⁺ basal epithelial cells that undergo a metabolic switch to aerobic glycolysis, resulting in lactate overproduction and microenvironment acidification. This acidic niche activates the proton-sensing receptor GPR68 on infiltrating CD4⁺ T cells, triggering a Gq–IP1–IKK/ERK signaling cascade that promotes Th2 differentiation and cytokine release. Genetic ablation of GPR68 in CD4⁺ T cells or its pharmacological inhibition with a natural antagonist, 3-Bn-6-Bnid-DKP, ameliorated type 2 inflammation and pathology in vivo. Thus, we define a lactate-GPR68 axis that metabolically couples epithelial dysfunction to adaptive type 2 immunity in ECRSwNP
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