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Int. J. Mol. Sci. 2014, 15(7), 12928-12939; doi:10.3390/ijms150712928
Article

WNT16B from Ovarian Fibroblasts Induces Differentiation of Regulatory T Cells through β-Catenin Signal in Dendritic Cells

1,†
,
1,†
,
2
,
1
,
3
,
1
,
2
 and
1,*
1 State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China 2 Affiliated Hospital of Luzhou Medical College, Luzhou 646000, China 3 Department of Medical Oncology, the Fifth People's Hospital of Chengdu, Chengdu 611130, China These authors contributed equally to this work.
* Author to whom correspondence should be addressed.
Received: 16 May 2014 / Revised: 4 July 2014 / Accepted: 14 July 2014 / Published: 21 July 2014
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
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Abstract

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 β-catenin in dendritic cells and secretion of interleukin-10 (IL-10) and transforming growth factor beta (TGF-β), 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.
Keywords: WNT16B; fibroblasts; regulatory T cells; dendritic cells; microenvironment WNT16B; fibroblasts; regulatory T cells; dendritic cells; microenvironment
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).
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Shen, C.-C.; Kang, Y.-H.; Zhao, M.; He, Y.; Cui, D.-D.; Fu, Y.-Y.; Yang, L.-L.; Gou, L.-T. WNT16B from Ovarian Fibroblasts Induces Differentiation of Regulatory T Cells through β-Catenin Signal in Dendritic Cells. Int. J. Mol. Sci. 2014, 15, 12928-12939.

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