The protein GATA-3 plays an important role in mammalian immune response, but its overall function in cell development and cancer formation is not well understood. In an effort to further define the importance of GATA-3, researchers at the University of North Carolina have traced how the protein performs important functions in CD8+T-cell type of the immune system.
GATA-3's role in CD4 T-cells has been widely studied, but its role in CD8+ cells has received much less attention. "We want to know what the basic function of GATA-3 in regulating cell biology is, although it has been shown that GATA-3 is important for the function of CD4+ T cell type to clear extracellular parasites," said Yisong Wan, PhD, assistant professor of microbiology and immunology at the UNC School of Medicine and member of UNC Lineberger Comprehensive Cancer Center.
The research, published online May 26 by Nature Immunology, shows that GATA-3 is required for the maintenance and function of CD8+ T-cells, a T-cell type mediating the immune response to clear pathogens, eradicate tumors and promote inflammation.
"If you delete that gene in a mouse, the mouse embryo fails to develop. It is involved in the developmental stages in many types of cells," said Wan.
Using mouse models with GATA-3 gene deleted only in T cells, the researchers found that while CD8+ cells can develop without GATA-3, the gene is indispensable for the continued maintenance and function of these T-cells. This new understanding of the links between GATA-3 and CD8+ cells will provide a greater understanding of immunoregulation and could assist in developing therapies for immunological diseases.
This study also found that GATA-3 regulates the signaling pathway that activates the oncogene c-MYC. GATA-3 has been linked to several types of tumors. "One of the markers for certain types of breast cancer is the up-regulation of GATA-3, and recently it has been associated with T-cell leukemia development" said Wan. "I wouldn't be surprised, and this is a bit of speculation, if GATA-3 may have a function in promoting certain breast cancer and T-cell leukemia through promoting the MYC pathway." said Wan. "If we are able to target GATA-3 in certain types of cancer, we may be able to suppress tumor formation."
This research was supported by NIH grant R01AI097392, National Multiple Sclerosis Society (RG4654) and the University Cancer Research Fund.
- Yunqi Wang, Ichiro Misumi, Ai-Di Gu, T Anthony Curtis, Lishan Su, Jason K Whitmire, Yisong Y Wan. GATA-3 controls the maintenance and proliferation of T cells downstream of TCR and cytokine signaling. Nature Immunology, 2013; DOI: 10.1038/ni.2623
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