IJMS, Vol. 15, Pages 12928-12939: WNT16B from Ovarian Fibroblasts Induces Differentiation of Regulatory T Cells through ?-Catenin Signal in Dendritic Cells (International Journal of Molecular Sciences)

Treatment for cancer can induce a series of secreted factors into the tumor microenvironment, which can affect cancer progression. Wingless-type MMTV (mouse mammary tumor virus) integration site 16B (WNT16B) is a new member of the WNT family and has been reported to play growth-related roles in previous studies. In this study, we found WNT16B could be expressed and secreted into the microenvironment by human ovarian fibroblasts after DNA damage-associated treatment, including chemotherapy drugs and radiation. We also demonstrated that fibroblast-derived WNT16B could result in accumulation of ?-catenin in dendritic cells and secretion of interleukin-10 (IL-10) and transforming growth factor beta (TGF-?), which contributed to the differentiation of regulatory T cells in a co-culture environment. These results shed light on the roles of WNT16B in immune regulation, especially in regard to cancer treatment.