Stat4 is expressed in activated peripheral blood monocytes, dendritic cells, and macrophages at sites of Th1-mediated inflammation.
Stat4 is a key transcription factor involved in promoting cell-mediated immunity, whose expression in mature cells has been reported to be restricted to T and NK cells. We demonstrate here, however, that Stat4 expression is not restricted to lymphoid cells. In their basal state, monocytes do not express Stat4. Upon activation, however, IFN-gamma- and LPS-treated monocytes and dendritic cells express high levels of Stat4. Monocyte-expressed Stat4 in humans is phosphorylated in response to IFN-alpha, but not IL-12. In contrast, the Th2 cytokines, IL-4 and IL-10, specifically down-regulate Stat4 expression in activated monocytes, while having little effect on Stat6 expression. Moreover, macrophages in synovial tissue obtained from patients with rheumatoid arthritis express Stat4 in vivo, suggesting a potential role in a prototypical Th1-mediated human disease. IFN-alpha-induced Stat4 activation in human monocytes represents a previously unrecognized signaling pathway at sites of Th1 inflammation.
Frucht
D M
DM
Lymphocyte Cell Biology Section, Arthritis and Rheumatism Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, MD 20892, USA.
Aringer
M
M
Galon
J
J
Danning
C
C
Brown
M
M
Fan
S
S
Centola
M
M
Wu
C Y
CY
Yamada
N
N
El Gabalawy
H
H
O'Shea
J J
JJ
D001172:Arthritis, Rheumatoid / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D016207:Cytokines / Q000502:physiology; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism*; D015536:Down-Regulation / Q000276:immunology; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology; D008262:Macrophage Activation; D008264:Macrophages / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D009000:Monocytes / Q000276:immunology / Q000378:metabolism*; D010766:Phosphorylation; D012333:RNA, Messenger / Q000096:biosynthesis / Q000097:blood; D050797:STAT4 Transcription Factor; D013583:Synovial Membrane / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology; D015534:Trans-Activators / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics
D016207:Cytokines; D004268:DNA-Binding Proteins; D016898:Interferon-alpha; D012333:RNA, Messenger; D050797:STAT4 Transcription Factor; C494090:STAT4 protein, human; D015534:Trans-Activators