| http://purl.uniprot.org/citations/21383241 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/21383241 | http://www.w3.org/2000/01/rdf-schema#comment | "Inhibitors of the JAK family of nonreceptor tyrosine kinases have demonstrated clinical efficacy in rheumatoid arthritis and other inflammatory disorders; however, the precise mechanisms by which JAK inhibition improves inflammatory immune responses remain unclear. In this study, we examined the mode of action of tofacitinib (CP-690,550) on JAK/STAT signaling pathways involved in adaptive and innate immune responses. To determine the extent of inhibition of specific JAK/STAT-dependent pathways, we analyzed cytokine stimulation of mouse and human T cells in vitro. We also investigated the consequences of CP-690,550 treatment on Th cell differentiation of naive murine CD4(+) T cells. CP-690,550 inhibited IL-4-dependent Th2 cell differentiation and interestingly also interfered with Th17 cell differentiation. Expression of IL-23 receptor and the Th17 cytokines IL-17A, IL-17F, and IL-22 were blocked when naive Th cells were stimulated with IL-6 and IL-23. In contrast, IL-17A production was enhanced when Th17 cells were differentiated in the presence of TGF-β. Moreover, CP-690,550 also prevented the activation of STAT1, induction of T-bet, and subsequent generation of Th1 cells. In a model of established arthritis, CP-690,550 rapidly improved disease by inhibiting the production of inflammatory mediators and suppressing STAT1-dependent genes in joint tissue. Furthermore, efficacy in this disease model correlated with the inhibition of both JAK1 and JAK3 signaling pathways. CP-690,550 also modulated innate responses to LPS in vivo through a mechanism likely involving the inhibition of STAT1 signaling. Thus, CP-690,550 may improve autoimmune diseases and prevent transplant rejection by suppressing the differentiation of pathogenic Th1 and Th17 cells as well as innate immune cell signaling."xsd:string |
| http://purl.uniprot.org/citations/21383241 | http://purl.org/dc/terms/identifier | "doi:10.4049/jimmunol.1003668"xsd:string |
| http://purl.uniprot.org/citations/21383241 | http://purl.uniprot.org/core/author | "Ghosh S."xsd:string |
| http://purl.uniprot.org/citations/21383241 | http://purl.uniprot.org/core/author | "Li X."xsd:string |
| http://purl.uniprot.org/citations/21383241 | http://purl.uniprot.org/core/author | "Tanaka M."xsd:string |
| http://purl.uniprot.org/citations/21383241 | http://purl.uniprot.org/core/author | "Thomas C.J."xsd:string |
| http://purl.uniprot.org/citations/21383241 | http://purl.uniprot.org/core/author | "Gadina M."xsd:string |
| http://purl.uniprot.org/citations/21383241 | http://purl.uniprot.org/core/author | "O'Shea J.J."xsd:string |
| http://purl.uniprot.org/citations/21383241 | http://purl.uniprot.org/core/author | "Lee J.L."xsd:string |
| http://purl.uniprot.org/citations/21383241 | http://purl.uniprot.org/core/author | "Minnerly J.C."xsd:string |
| http://purl.uniprot.org/citations/21383241 | http://purl.uniprot.org/core/author | "Ghoreschi K."xsd:string |
| http://purl.uniprot.org/citations/21383241 | http://purl.uniprot.org/core/author | "Kishore N."xsd:string |
| http://purl.uniprot.org/citations/21383241 | http://purl.uniprot.org/core/author | "Radi Z.A."xsd:string |
| http://purl.uniprot.org/citations/21383241 | http://purl.uniprot.org/core/author | "Dowty M.E."xsd:string |
| http://purl.uniprot.org/citations/21383241 | http://purl.uniprot.org/core/author | "Storer C.E."xsd:string |
| http://purl.uniprot.org/citations/21383241 | http://purl.uniprot.org/core/author | "Head R.D."xsd:string |
| http://purl.uniprot.org/citations/21383241 | http://purl.uniprot.org/core/author | "Jesson M.I."xsd:string |
| http://purl.uniprot.org/citations/21383241 | http://purl.uniprot.org/core/author | "LaBranche T.P."xsd:string |
| http://purl.uniprot.org/citations/21383241 | http://purl.uniprot.org/core/author | "Meyer D.M."xsd:string |
| http://purl.uniprot.org/citations/21383241 | http://purl.uniprot.org/core/author | "Steward-Tharp S.M."xsd:string |
| http://purl.uniprot.org/citations/21383241 | http://purl.uniprot.org/core/author | "Alsup J.W."xsd:string |
| http://purl.uniprot.org/citations/21383241 | http://purl.uniprot.org/core/author | "Warner J.D."xsd:string |
| http://purl.uniprot.org/citations/21383241 | http://purl.uniprot.org/core/date | "2011"xsd:gYear |
| http://purl.uniprot.org/citations/21383241 | http://purl.uniprot.org/core/name | "J Immunol"xsd:string |