Matches in SemOpenAlex for { <https://semopenalex.org/work/W4200255118> ?p ?o ?g. }
- W4200255118 abstract "Psoriasis is a complex chronic inflammatory skin disease with unclear molecular mechanisms. We found that the Src homology-2 domain-containing protein tyrosine phosphatase-2 (SHP2) was highly expressed in both psoriatic patients and imiquimod (IMQ)-induced psoriasis-like mice. Also, the SHP2 allosteric inhibitor SHP099 reduced pro-inflammatory cytokine expression in PBMCs taken from psoriatic patients. Consistently, SHP099 significantly ameliorated IMQ-triggered skin inflammation in mice. Single-cell RNA sequencing of murine skin demonstrated that SHP2 inhibition impaired skin inflammation in myeloid cells, especially macrophages. Furthermore, IMQ-induced psoriasis-like skin inflammation was significantly alleviated in myeloid cells (monocytes, mature macrophages, and granulocytes)-but not dendritic cells conditional SHP2 knockout mice. Mechanistically, SHP2 promoted the trafficking of toll-like receptor 7 (TLR7) from the Golgi to the endosome in macrophages by dephosphorylating TLR7 at Tyr1024, boosting the ubiquitination of TLR7 and NF-κB-mediated skin inflammation. Importantly, Tlr7 point-mutant knock-in mice showed an attenuated psoriasis-like phenotype compared to wild-type littermates following IMQ treatment. Collectively, our findings identify SHP2 as a novel regulator of psoriasis and suggest that SHP2 inhibition may be a promising therapeutic approach for psoriatic patients." @default.
- W4200255118 created "2021-12-31" @default.
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- W4200255118 date "2021-12-22" @default.
- W4200255118 modified "2023-10-14" @default.
- W4200255118 title "Allosteric inhibition of SHP2 uncovers aberrant TLR7 trafficking in aggravating psoriasis" @default.
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- W4200255118 cites W1974362693 @default.
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- W4200255118 cites W1998448154 @default.
- W4200255118 cites W1998541797 @default.
- W4200255118 cites W2022168094 @default.
- W4200255118 cites W2030223949 @default.
- W4200255118 cites W2035618305 @default.
- W4200255118 cites W2036560307 @default.
- W4200255118 cites W2041820695 @default.
- W4200255118 cites W2043160859 @default.
- W4200255118 cites W2054230488 @default.
- W4200255118 cites W2058863496 @default.
- W4200255118 cites W2060351820 @default.
- W4200255118 cites W2079776221 @default.
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- W4200255118 cites W2335131782 @default.
- W4200255118 cites W2371463409 @default.
- W4200255118 cites W2414878307 @default.
- W4200255118 cites W2468923062 @default.
- W4200255118 cites W2506275367 @default.
- W4200255118 cites W2514306162 @default.
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- W4200255118 cites W2604840810 @default.
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- W4200255118 cites W2775320826 @default.
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- W4200255118 cites W3007192247 @default.
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- W4200255118 doi "https://doi.org/10.15252/emmm.202114455" @default.
- W4200255118 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/34936223" @default.
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