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| Subject | Predicate | Object |
|---|---|---|
| http://purl.uniprot.org/citations/33649184 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/33649184 | http://www.w3.org/2000/01/rdf-schema#comment | "Kv1.3 potassium channels, expressed by proinflammatory central nervous system mononuclear phagocytes (CNS-MPs), are promising therapeutic targets for modulating neuroinflammation in Alzheimer's disease (AD). The molecular characteristics of Kv1.3-high CNS-MPs and their cellular origin from microglia or CNS-infiltrating monocytes are unclear. While Kv1.3 blockade reduces amyloid beta (Aβ) burden in mouse models, the downstream immune effects on molecular profiles of CNS-MPs remain unknown. We show that functional Kv1.3 channels are selectively expressed by a subset of CD11b+CD45+ CNS-MPs acutely isolated from an Aβ mouse model (5xFAD) as well as fresh postmortem human AD brain. Transcriptomic profiling of purified CD11b+Kv1.3+ CNS-MPs, CD11b+CD45int Kv1.3neg microglia, and peripheral monocytes from 5xFAD mice revealed that Kv1.3-high CNS-MPs highly express canonical microglial markers (Tmem119, P2ry12) and are distinct from peripheral Ly6chigh/Ly6clow monocytes. Unlike homeostatic microglia, Kv1.3-high CNS-MPs express relatively lower levels of homeostatic genes, higher levels of CD11c, and increased levels of glutamatergic transcripts, potentially representing phagocytic uptake of neuronal elements. Using irradiation bone marrow CD45.1/CD45.2 chimerism in 5xFAD mice, we show that Kv1.3+ CNS-MPs originate from microglia and not blood-derived monocytes. We show that Kv1.3 channels regulate membrane potential and early signaling events in microglia. Finally, in vivo blockade of Kv1.3 channels in 5xFAD mice by ShK-223 reduced Aβ burden, increased CD11c+ CNS-MPs, and expression of phagocytic genes while suppressing proinflammatory genes (IL1b). Our results confirm the microglial origin and identify unique molecular features of Kv1.3-expressing CNS-MPs. In addition, we provide evidence for CNS immunomodulation by Kv1.3 blockers in AD mouse models resulting in a prophagocytic phenotype."xsd:string |
| http://purl.uniprot.org/citations/33649184 | http://purl.org/dc/terms/identifier | "doi:10.1073/pnas.2013545118"xsd:string |
| http://purl.uniprot.org/citations/33649184 | http://purl.uniprot.org/core/author | "Chen M.J."xsd:string |
| http://purl.uniprot.org/citations/33649184 | http://purl.uniprot.org/core/author | "Gao T."xsd:string |
| http://purl.uniprot.org/citations/33649184 | http://purl.uniprot.org/core/author | "Levey A.I."xsd:string |
| http://purl.uniprot.org/citations/33649184 | http://purl.uniprot.org/core/author | "Xiao H."xsd:string |
| http://purl.uniprot.org/citations/33649184 | http://purl.uniprot.org/core/author | "Nguyen H.M."xsd:string |
| http://purl.uniprot.org/citations/33649184 | http://purl.uniprot.org/core/author | "Wulff H."xsd:string |
| http://purl.uniprot.org/citations/33649184 | http://purl.uniprot.org/core/author | "Galipeau J."xsd:string |
| http://purl.uniprot.org/citations/33649184 | http://purl.uniprot.org/core/author | "Pennati A."xsd:string |
| http://purl.uniprot.org/citations/33649184 | http://purl.uniprot.org/core/author | "Dammer E.B."xsd:string |
| http://purl.uniprot.org/citations/33649184 | http://purl.uniprot.org/core/author | "Rangaraju S."xsd:string |
| http://purl.uniprot.org/citations/33649184 | http://purl.uniprot.org/core/author | "Rayaprolu S."xsd:string |
| http://purl.uniprot.org/citations/33649184 | http://purl.uniprot.org/core/author | "Waller E.K."xsd:string |
| http://purl.uniprot.org/citations/33649184 | http://purl.uniprot.org/core/author | "Seyfried N.T."xsd:string |
| http://purl.uniprot.org/citations/33649184 | http://purl.uniprot.org/core/author | "Katz D.J."xsd:string |
| http://purl.uniprot.org/citations/33649184 | http://purl.uniprot.org/core/author | "Giver C.R."xsd:string |
| http://purl.uniprot.org/citations/33649184 | http://purl.uniprot.org/core/author | "Bowen C.A."xsd:string |
| http://purl.uniprot.org/citations/33649184 | http://purl.uniprot.org/core/author | "Engstrom A.K."xsd:string |
| http://purl.uniprot.org/citations/33649184 | http://purl.uniprot.org/core/author | "Wood L.B."xsd:string |
| http://purl.uniprot.org/citations/33649184 | http://purl.uniprot.org/core/author | "Bitarafan S."xsd:string |
| http://purl.uniprot.org/citations/33649184 | http://purl.uniprot.org/core/author | "Nwabueze N."xsd:string |
| http://purl.uniprot.org/citations/33649184 | http://purl.uniprot.org/core/author | "Ramesha S."xsd:string |
| http://purl.uniprot.org/citations/33649184 | http://purl.uniprot.org/core/date | "2021"xsd:gYear |