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

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.     

Significant Roles of Regulatory T Cells and Myeloid Derived Suppressor Cells in Hepatitis B Virus Persistent Infection and Hepatitis B Virus-Related HCCs

The adaptive immune system, including type1 helper T cells (Th1 cells), cytotoxic T lymphocytes (CTLs), and dendritic cells (DCs), plays an important role in the control of hepatitis B virus (HBV). On the other hand, regulatory T cells (Tregs) and myeloid derived suppressor cells (MDSCs) suppress the immune reaction in HBV and hepatocellular carcinoma (HCC). Excessive activation of immune suppressive cells could contribute to the persistent infection of HBV and the progression of HCC. The frequency and/or function of Tregs could affect the natural course in chronic hepatitis B patients and the treatment response. In addition to the suppressive function of MDSCs, MDSCs could affect the induction and function of Tregs. Therefore, we should understand in detail the mechanism by which Tregs and MDSCs are induced to control HBV persistent infection and HBV-related HCC. Immune suppressive cells, including Tregs and MDSCs, contribute to the difficulty in inducing an effective immune response for HBV persistent infection and HBV-related HCC. In this review, we focus on the Tregs and MDSCs that could be potential targets for immune therapy of chronic hepatitis B and HBV-related HCC.     

Galectin-9 Induced Myeloid Suppressor Cells Expand Regulatory T Cells in an IL-10-Dependent Manner in CVB3-Induced Acute Myocarditis

The objective of the study was to explore the effects of galectin-9 on myeloid suppressor cells in Coxsackievirus B3 (CVB3)-induced myocarditis and the possible mechanisms involved. For this purpose, BALB/c male mice were infected with CVB3 on day 0 and then received intraperitoneal (IP) administration of recombinant galectin-9 or phosphate-buffered saline (PBS) daily from day 3 to day 7. The phenotypes and functions of myeloid suppressor cells were evaluated. The role and mechanism of myeloid suppressor cells and subsets in CVB3-induced myocarditis in vitro were explored. We found that galectin-9 remarkably increased the frequencies of CD11b⁺Gr-1⁺ cells in the cardiac tissue and spleen with myocarditis. Ly-6G⁺ cells were decreased and Ly-6C⁺ cells were increased in galectin-9-treated mice. In addition, CD11b⁺Gr-1⁺ cells were highly effective in suppressing CD4⁺ T cells. Moreover, our data demonstrate that CD11b⁺Gr-1⁺ cells are capable of expanding regulatory T cells (Tregs) from a preexisting population of natural Tregs, which depends on IL-10 but not TGF-β. Our results indicate that galectin-9 therapy may represent a useful approach to ameliorate CVB3-induced myocarditis.