X. O. Yang et al., "STAT3 regulates cytokine-mediated generation of inflammatory helper T cells," J Biol Chem, 282:9358–63, 2007. (Cited in 118 papers)
Chen Dong and his colleagues at the M.D. Anderson Cancer Center in Houston, Texas, modulated the expression levels of a transcription factor called STAT3 in undifferentiated helper T cells from mice spleen and lymph nodes. They showed that STAT3 is essential for the differentiation of TH17, a recently discovered helper T cell so-named because it produces the cytokine interleukin-17 (IL-17).
IL-17 has been implicated in a variety of inflammatory diseases, including multiple sclerosis, psoriasis, and rheumatoid arthritis. The recognition of STAT3's role in TH17's development "identifies a clear drug target to inhibit TH17 differentiation," says Jay Kolls, an immunologist at Louisiana State University in New Orleans.
"The genome-wide targets...
The next step is to determine what else STAT3 is doing, O'Shea says. With more information about the mechanism of STAT3's regulatory properties, it should be possible to target molecules further downstream in the pathway to successfully treat certain diseases without disrupting other cellular functions. "Many groups are working on it," says Dong.
|Changes in IL-17 cytokine expression from normal levels|
|STAT 3 overexpressed with retroviral vectors: 1.93-fold increase|
|STAT 3 null mutant: 26.91-fold decrease|