Inhibiting ex-vivo Th17 responses in Ankylosing Spondylitis by targeting Janus kinases.
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Your vote was cast
Thank you for your feedback
Thank you for your feedback
de Wit, Jelle
Al-Mossawi, M Hussein
MetadataShow full item record
TitleInhibiting ex-vivo Th17 responses in Ankylosing Spondylitis by targeting Janus kinases.
Published inSci Rep 2018; 8(1):15645
PubliekssamenvattingTreatment options for Ankylosing Spondylitis (AS) are still limited. The T helper cell 17 (Th17) pathway has emerged as a major driver of disease pathogenesis and a good treatment target. Janus kinases (JAK) are key transducers of cytokine signals in Th17 cells and therefore promising targets for the treatment of AS. Here we investigate the therapeutic potential of four different JAK inhibitors on cells derived from AS patients and healthy controls, cultured in-vitro under Th17-promoting conditions. Levels of IL-17A, IL-17F, IL-22, GM-CSF and IFNγ were assessed by ELISA and inhibitory effects were investigated with Phosphoflow. JAK1/2/3 and TYK2 were silenced in CD4+ T cells with siRNA and effects analyzed by ELISA (IL-17A, IL-17F and IL-22), Western Blot, qPCR and Phosphoflow. In-vitro inhibition of CD4+ T lymphocyte production of multiple Th17 cytokines (IL-17A, IL-17F and IL-22) was achieved with JAK inhibitors of differing specificity, as well as by silencing of JAK1-3 and Tyk2, without impacting on cell viability or proliferation. Our preclinical data suggest JAK inhibitors as promising candidates for therapeutic trials in AS, since they can inhibit multiple Th17 cytokines simultaneously. Improved targeting of TYK2 or other JAK isoforms may confer tailored effects on Th17 responses in AS.
The following license files are associated with this item:
- Creative Commons
Except where otherwise noted, this item's license is described as Archived with thanks to Scientific reports
- Selective targeting of PI3Kδ suppresses human IL-17-producing T cells and innate-like lymphocytes and may be therapeutic for IL-17-mediated diseases.
- Authors: Chen S, Paveley R, Kraal L, Sritharan L, Stevens E, Dedi N, Shock A, Shaw S, Juarez M, Yeremenko N, Baeten D, Payne A
- Issue date: 2020 Jul
- TSLP Produced by Aspergillus fumigatus-Stimulated DCs Promotes a Th17 Response Through the JAK/STAT Signaling Pathway in Fungal Keratitis.
- Authors: Han F, Guo H, Wang L, Zhang Y, Sun L, Dai C, Wu X
- Issue date: 2020 Dec 1
- Heme oxygenase-1 directly binds STAT3 to control the generation of pathogenic Th17 cells during neutrophilic airway inflammation.
- Authors: Lin XL, Lv JJ, Lv J, Di CX, Zhang YJ, Zhou T, Liu JL, Xia ZW
- Issue date: 2017 Dec
- BJ-2266 ameliorates experimental autoimmune encephalomyelitis through down-regulation of the JAK/STAT signaling pathway.
- Authors: You Z, Timilshina M, Jeong BS, Chang JH
- Issue date: 2017 Sep
- Withasteroid B from D. metel L. regulates immune responses by modulating the JAK/STAT pathway and the IL-17<sup>+</sup> RORγt<sup>+</sup> /IL-10<sup>+</sup> FoxP3<sup>+</sup> ratio.
- Authors: Su Y, Wang Q, Yang B, Wu L, Cheng G, Kuang H
- Issue date: 2017 Oct