FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W4383106486> ?p ?o ?g. }

• W4383106486 abstract "Abstract Background The activation of CD8 + T cells and their trafficking to the skin through JAK-STAT signaling play a central role in the development of vitiligo. Thus, targeting this key disease pathway with innovative drugs is an effective strategy for treating vitiligo. Natural products isolated from medicinal herbs are a useful source of novel therapeutics. Demethylzeylasteral (T-96), extracted from Tripterygium wilfordii Hook F, possesses immunosuppressive and anti-inflammatory properties. Methods The efficacy of T-96 was tested in our mouse model of vitiligo, and the numbers of CD8 + T cells infiltration and melanocytes remaining in the epidermis were quantified using whole-mount tail staining. Immune regulation of T-96 in CD8 + T cells was evaluated using flow cytometry. Pull-down assay, mass spectrum analysis, molecular docking, knockdown and overexpression approaches were utilized to identify the target proteins of T-96 in CD8 + T cells and keratinocytes. Results Here, we found that T-96 reduced CD8 + T cell infiltration in the epidermis using whole-mount tail staining and alleviated the extent of depigmentation to a comparable degree of tofacitinib (Tofa) in our vitiligo mouse model. In vitro, T-96 decreased the proliferation, CD69 membrane expression, and IFN-γ, granzyme B, (GzmB), and perforin (PRF) levels in CD8 + T cells isolated from patients with vitiligo. Pull-down assays combined with mass spectrum analysis and molecular docking showed that T-96 interacted with JAK3 in CD8 + T cell lysates. Furthermore, T-96 reduced JAK3 and STAT5 phosphorylation following IL-2 treatment. T-96 could not further reduce IFN-γ, GzmB and PRF expression following JAK3 knockdown or inhibit increased immune effectors expression upon JAK3 overexpression. Additionally, T-96 interacted with JAK2 in IFN-γ-stimulated keratinocytes, inhibiting the activation of JAK2, decreasing the total and phosphorylated protein levels of STAT1, and reducing the production and secretion of CXCL9 and CXCL10. T-96 did not significantly inhibit STAT1 and CXCL9/10 expression following JAK2 knockdown, nor did it suppress upregulated STAT1-CXCL9/10 signaling upon JAK2 overexpression. Finally, T-96 reduced the membrane expression of CXCR3, and the culture supernatants pretreated with T-96 under IFN-γ stressed keratinocytes markedly blocked the migration of CXCR3 + CD8 + T cells, similarly to Tofa in vitro. Conclusion Our findings demonstrated that T-96 might have positive therapeutic responses to vitiligo by pharmacologically inhibiting the effector functions and skin trafficking of CD8 + T cells through JAK-STAT signaling." @default.
• W4383106486 created "2023-07-05" @default.
• W4383106486 creator A5009573286 @default.
• W4383106486 creator A5013475774 @default.
• W4383106486 creator A5014774434 @default.
• W4383106486 creator A5020323904 @default.
• W4383106486 creator A5023006263 @default.
• W4383106486 creator A5043178413 @default.
• W4383106486 creator A5047013876 @default.
• W4383106486 creator A5062292067 @default.
• W4383106486 creator A5066455099 @default.
• W4383106486 creator A5084195289 @default.
• W4383106486 creator A5084363347 @default.
• W4383106486 date "2023-07-04" @default.
• W4383106486 modified "2023-10-15" @default.
• W4383106486 title "Pharmacological inhibition of demethylzeylasteral on JAK-STAT signaling ameliorates vitiligo" @default.
• W4383106486 cites W1494514268 @default.
• W4383106486 cites W1646626736 @default.
• W4383106486 cites W1839693730 @default.
• W4383106486 cites W1973454407 @default.
• W4383106486 cites W1981393767 @default.
• W4383106486 cites W1995078506 @default.
• W4383106486 cites W1995362507 @default.
• W4383106486 cites W2000055033 @default.
• W4383106486 cites W2007239568 @default.
• W4383106486 cites W2052860776 @default.
• W4383106486 cites W2060069128 @default.
• W4383106486 cites W2086121828 @default.
• W4383106486 cites W2139070921 @default.
• W4383106486 cites W2143968342 @default.
• W4383106486 cites W2294910886 @default.
• W4383106486 cites W2395581755 @default.
• W4383106486 cites W2403144801 @default.
• W4383106486 cites W2410712898 @default.
• W4383106486 cites W2524233274 @default.
• W4383106486 cites W2554784349 @default.
• W4383106486 cites W2558494406 @default.
• W4383106486 cites W2581360967 @default.
• W4383106486 cites W2583402497 @default.
• W4383106486 cites W2595511842 @default.
• W4383106486 cites W2605716087 @default.
• W4383106486 cites W2614534012 @default.
• W4383106486 cites W2626458389 @default.
• W4383106486 cites W2765827083 @default.
• W4383106486 cites W2773389864 @default.
• W4383106486 cites W2790481979 @default.
• W4383106486 cites W2799273836 @default.
• W4383106486 cites W2808825101 @default.
• W4383106486 cites W2896920177 @default.
• W4383106486 cites W2897972877 @default.
• W4383106486 cites W2912966489 @default.
• W4383106486 cites W2913065725 @default.
• W4383106486 cites W2939514948 @default.
• W4383106486 cites W2943840241 @default.
• W4383106486 cites W2944059399 @default.
• W4383106486 cites W2949094282 @default.
• W4383106486 cites W2975860655 @default.
• W4383106486 cites W2978270418 @default.
• W4383106486 cites W2979754363 @default.
• W4383106486 cites W2980286352 @default.
• W4383106486 cites W2984019502 @default.
• W4383106486 cites W2984536867 @default.
• W4383106486 cites W3004467513 @default.
• W4383106486 cites W3008324271 @default.
• W4383106486 cites W3008956037 @default.
• W4383106486 cites W3012377065 @default.
• W4383106486 cites W3012531490 @default.
• W4383106486 cites W3015033846 @default.
• W4383106486 cites W3041952258 @default.
• W4383106486 cites W3084335294 @default.
• W4383106486 cites W3087189378 @default.
• W4383106486 cites W3099539338 @default.
• W4383106486 cites W3111996400 @default.
• W4383106486 cites W3114894293 @default.
• W4383106486 cites W3115761475 @default.
• W4383106486 cites W3161323196 @default.
• W4383106486 cites W3171018229 @default.
• W4383106486 cites W3205210147 @default.
• W4383106486 cites W4200436377 @default.
• W4383106486 cites W4224246419 @default.
• W4383106486 doi "https://doi.org/10.1186/s12967-023-04293-2" @default.
• W4383106486 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/37403086" @default.
• W4383106486 hasPublicationYear "2023" @default.
• W4383106486 type Work @default.
• W4383106486 citedByCount "0" @default.
• W4383106486 crossrefType "journal-article" @default.
• W4383106486 hasAuthorship W4383106486A5009573286 @default.
• W4383106486 hasAuthorship W4383106486A5013475774 @default.
• W4383106486 hasAuthorship W4383106486A5014774434 @default.
• W4383106486 hasAuthorship W4383106486A5020323904 @default.
• W4383106486 hasAuthorship W4383106486A5023006263 @default.
• W4383106486 hasAuthorship W4383106486A5043178413 @default.
• W4383106486 hasAuthorship W4383106486A5047013876 @default.
• W4383106486 hasAuthorship W4383106486A5062292067 @default.
• W4383106486 hasAuthorship W4383106486A5066455099 @default.
• W4383106486 hasAuthorship W4383106486A5084195289 @default.
• W4383106486 hasAuthorship W4383106486A5084363347 @default.
• W4383106486 hasBestOaLocation W43831064861 @default.
• W4383106486 hasConcept C154317977 @default.
• W4383106486 hasConcept C167672396 @default.

• next