Stat4 is expressed in activated peripheral blood monocytes, dendritic cells, and macrophages at sites of Th1-mediated inflammation

D M Frucht; M Aringer; J Galon; C Danning; M Brown; S Fan; M Centola; C Y Wu; N Yamada; H El Gabalawy; J J O'Shea

doi:10.4049/jimmunol.164.9.4659

Stat4 is expressed in activated peripheral blood monocytes, dendritic cells, and macrophages at sites of Th1-mediated inflammation

J Immunol. 2000 May 1;164(9):4659-64. doi: 10.4049/jimmunol.164.9.4659.

Authors

D M Frucht¹, M Aringer, J Galon, C Danning, M Brown, S Fan, M Centola, C Y Wu, N Yamada, H El Gabalawy, J J O'Shea

Affiliation

¹ Lymphocyte Cell Biology Section, Arthritis and Rheumatism Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, MD 20892, USA.

PMID: 10779770
DOI: 10.4049/jimmunol.164.9.4659

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Arthritis, Rheumatoid / immunology
Arthritis, Rheumatoid / metabolism
Arthritis, Rheumatoid / pathology*
Cytokines / physiology
DNA-Binding Proteins / antagonists & inhibitors
DNA-Binding Proteins / biosynthesis*
DNA-Binding Proteins / blood
DNA-Binding Proteins / genetics
Dendritic Cells / immunology
Dendritic Cells / metabolism*
Down-Regulation / immunology
Humans
Interferon-alpha / pharmacology
Macrophage Activation*
Macrophages / immunology
Macrophages / metabolism*
Macrophages / pathology
Monocytes / immunology
Monocytes / metabolism*
Phosphorylation
RNA, Messenger / biosynthesis
RNA, Messenger / blood
STAT4 Transcription Factor
Synovial Membrane / immunology
Synovial Membrane / metabolism
Synovial Membrane / pathology
Th1 Cells / immunology*
Th1 Cells / metabolism
Th2 Cells / immunology
Trans-Activators / antagonists & inhibitors
Trans-Activators / biosynthesis*
Trans-Activators / blood
Trans-Activators / genetics

Substances

Cytokines
DNA-Binding Proteins
Interferon-alpha
RNA, Messenger
STAT4 Transcription Factor
STAT4 protein, human
Trans-Activators