title: Inhibitory effects of the JAK inhibitor CP690,550 on human CD4(+) T lymphocyte cytokine production.
abstract: BACKGROUND
  The new JAK3 inhibitor, CP690,550, has shown efficacy in the treatment of rheumatoid arthritis. The present study was undertaken to assess the effects of CP690,550 on cytokine production and cellular signaling in human CD4(+) T cells.
  
  
  RESULTS
  CD4(+) T cells produced IL-2, IL-4, IL-17, IL-22 and IFN-γ in following stimulation with a CD3 antibody. At the optimal concentration, CP690,550 almost completely inhibited the production of IL-4, IL-17, IL-22 and IFN-γ from these activated CD4(+) T cells, but only had marginal effects on IL-2 production. Moreover CP690,550 inhibited anti-CD3-induced phosphorylation of STAT1, STAT3, STAT4, STAT5, and STAT6, but not the TCR-associated phosphorylation of ZAP-70.
  
  
  CONCLUSIONS
  Therefore, CP690,550-mediated modification of the JAK/STAT pathway may be a new immunosuppressive strategy in the treatment of autoimmune diseases.
authors: Department of Rheumatology and Clinical Research Center, NHO Nagasaki Medical Center, Kubara 2-1001-1, Omura 856-8652, Japan. migita@nmc.hosp.go.jp
authors: Kiyoshi
authors: K
authors: Migita
authors: Taiichiro
authors: T
authors: Miyashita
authors: Yasumori
authors: Y
authors: Izumi
authors: Tomohiro
authors: T
authors: Koga
authors: Atsumasa
authors: A
authors: Komori
authors: Yumi
authors: Y
authors: Maeda
authors: Yuka
authors: Y
authors: Jiuchi
authors: Yoshihiro
authors: Y
authors: Aiba
authors: Satoshi
authors: S
authors: Yamasaki
authors: Atsushi
authors: A
authors: Kawakami
authors: Minoru
authors: M
authors: Nakamura
authors: Hiromi
authors: H
authors: Ishibashi
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology / Q000378:metabolism; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000276:immunology*; D017252:CD3 Complex / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D007165:Immunosuppression Therapy; D053616:Janus Kinase 3 / Q000037:antagonists & inhibitors*; D008213:Lymphocyte Activation / Q000187:drug effects; D010766:Phosphorylation; D010880:Piperidines; D011743:Pyrimidines / Q000494:pharmacology*; D011758:Pyrroles / Q000494:pharmacology*; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D050791:STAT Transcription Factors / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D017252:CD3 Complex; D016207:Cytokines; D010880:Piperidines; D011743:Pyrimidines; D011758:Pyrroles; D011948:Receptors, Antigen, T-Cell; D050791:STAT Transcription Factors; C479163:tofacitinib; D053616:Janus Kinase 3