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• W3091501988 abstract "SUMMARY Psoriasis is a complex chronic inflammatory skin disease with unclear molecular mechanisms. Here, we identify Src homology-2 domain containing protein tyrosine phosphatase-2 (SHP2) as a novel accelerator of psoriasis development. Both genetic ablation of SHP2 in macrophages and pharmacological inhibition of SHP2 prevents the development of psoriasis-like skin inflammation in an imiquimod-induced murine model of psoriasis. Mechanistically, SHP2 promotes the trafficking of Toll-like receptor 7 (TLR7) from Golgi to endosome through its interaction with and dephosphorylation of TLR7 at Tyr1024, which promotes the ubiquitination of TLR7 and psoriasis-like skin inflammation. Importantly, SHP2 allosteric inhibitor SHP099 reduces the expression of pro-inflammatory cytokines in peripheral blood mononuclear cells from human patients with psoriasis. 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.
• W3091501988 created "2020-10-08" @default.
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• W3091501988 date "2020-09-30" @default.
• W3091501988 modified "2023-10-16" @default.
• W3091501988 title "Inhibition of SHP2 ameliorates psoriasis by decreasing TLR7 endosome localization" @default.
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• W3091501988 doi "https://doi.org/10.1101/2020.09.28.20202861" @default.
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