Immune Cells STAT4 in Myeloid Cells-Implications for Autoimmunity

STAT4 is a transcription factor whose expression and activation is critical for the differentiation and expansion of type 1 T helper cells (Th1) cells, which regulate cell-mediated immunity. Although STAT4 expression was thought to be limited to cells of lymphocytic lineage, Frucht et al. demonstrate that STAT4 is produced in activated human monocytes and dendritic cells, and that its expression depends on prior treatment with lipopolysaccharide, interferon- (IFN-), or both. STAT4 expression was attenuated by incubation with either of the Th2 cytokines interleukin 4 (IL-4) or IL-10. Whereas STAT4 from murine monocytes is activated by IL-12 or IFN-α, Frucht et al. demonstrate that STAT4 from human monocytes was activated and tyrosine phosphorylated in an IFN-α-dependent manner. IL-12 was unable to activate STAT4 in human monocytes, which correlated with a complete absence of expressed IL-12 receptor (IL-12R) β2 protein, a critical component of the IL-12R. Macrophages derived from the synovial tissue of rheumatoid arthritis patients were found to express STAT4, indicating that the macrophages were activated and that STAT4 is expressed at inflammatory sites in vivo. Although the functional role of STAT4 in human monocytes remains unknown, the eventual identification of STAT4-dependent genes in monocytes may clarify the role of STAT4 in these cells. Similarly, activated STAT4 in myeloid cells may provide a target for new immune therapies.

Frucht, D.M., Aringer, M., Galon, J., Danning, C., Brown, M., Fan, S., Centola, M., Wu, C.-Y., Yamada, N., El Gabalawy, H., and O'Shea, J.J. (2000) Stat4 is expressed in activated peripheral blood monocytes, dendritic cells, and macrophages at sites of Th1-mediated inflammation. J. Immunol. 164: 4659-4664. [Online Journal]