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Lymphocyte Cell Biology Section,
Clinical Research Group, and
Genetics Section, Arthritis and Rheumatism Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, MD 20892;
§
Experimental Immunology Branch and
¶
Dermatology Branch, National Cancer Institute, Bethesda, MD 20892; and
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Laboratory of Clinical Investigation, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892
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-
- and LPS-treated monocytes and dendritic cells express
high levels of Stat4. Monocyte-expressed Stat4 in humans is
phosphorylated in response to IFN-
, 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--induced Stat4 activation in human monocytes represents a
previously unrecognized signaling pathway at sites of Th1
inflammation.
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