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 imm unity, whose expression in mature cells has been reported to be restricted to T and NK cells. We demonstrate here, however, that Stat4 expression is n ot restricted to lymphoid cells. In their basal state, monocytes do not exp ress 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 con trast, the Th2 cytokines, IL-4 and IL-10, specifically down-regulate Stat4 expression in activated monocytes, while having little effect on Stat6 expr ession. Moreover, macrophages in synovial tissue obtained from patients wit h rheumatoid arthritis express Stat4 in vivo, suggesting a potential role i n a prototypical Th1-mediated human disease. IFN-alpha -induced Stat4 activ ation in human monocytes represents a previously unrecognized signaling pat hway at sites of Th1 inflammation.