Suppressive influences of IFN-alpha on IL-17 expression in human CD4+ T cells.
We examined the direct effects of IFN-alpha on the development of Th17 with a system using immobilized anti-CD3, which permits activation of CD4+ T cells in the complete absence of accessory cells. Highly purified CD4+ T cells obtained from healthy donors were stimulated with immobilized anti-CD3 with or without IFN-alpha. IFN-alpha suppressed the production of IL-17 of immobilized anti-CD3-stimulated CD4+ T cells in a dose-response manner. Accordingly, IFN-alpha inhibited IL-17 mRNA expression in immobilized anti-CD3-stimulated CD4+ T cells. IFN-alpha did not affect the production of TGF-beta or IL-6, but inhibited RORC mRNA expression of anti-CD3-stimulated CD4+ T cells. These results indicate that IFN-alpha suppresses IL-17 expression and Th17 differentiation through down-regulation of RORC mRNA expression. It is therefore suggested that these effects might play a role in the mode of action of IFN-alpha in the treatment of various inflammatory diseases.
Hirohata
Shunsei
S
Department of Rheumatology and Infectious Diseases, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan. shunsei_tenpoint@yahoo.co.jp
Shibuya
Hideki
H
Tejima
Satoko
S
D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology*; D015536:Down-Regulation / Q000187:drug effects / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D016898:Interferon-alpha / Q000276:immunology / Q000494:pharmacology*; D020381:Interleukin-17 / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D015850:Interleukin-6 / Q000276:immunology; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018709:Statistics, Nonparametric; D016212:Transforming Growth Factor beta / Q000276:immunology
D016898:Interferon-alpha; D020381:Interleukin-17; D015850:Interleukin-6; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D012333:RNA, Messenger; C539900:RORC protein, human; D016212:Transforming Growth Factor beta