ABSTRACT
BACKGROUND: Documented reports proved that Epstein-Barr virus (EBV) infection increased infiltration of Tregs in malignancy. However, the mechanism of EBV recruitment Tregs into nasopharyngeal carcinoma (NPC) tissues has not been detailed discussion. METHODS: Expression of EBV nuclear antigen 1 (EBNA1) and Foxp3 in NPC tissue samples was detected by immunohistochemistry. EBNA1+ NPC cell lines were used to coculture with PBMC, naïve T cells, Tregs, and monocytes. Percent of Treg was detected by flow cytometry. RESULTS: EBNA1 protein was overexpressed in NPC tissues, and was associated with a number of infiltrated Tregs. EBNA1+ NPC cells converted naïve T cells into Tregs by up-regulated TGF-ß1. Enhanced CCL20 production in EBNA1-expressed tumor cells increased Tregs migration. Polarized-M2 macrophages by EBNA1 expression cells converted naïve T cells into Tregs. CONCLUSIONS: EBNA1 favors accumulation of Tregs in NPC through: (a) upregulated TGF-ß1 converted naïve T cell into Treg; (b) upregulated CCL20 increased Treg migration; and (c) polarized-M2 macrophage converted naïve T cell into Treg.
Subject(s)
Epstein-Barr Virus Nuclear Antigens/genetics , Nasopharyngeal Carcinoma/genetics , Adult , Cell Line, Tumor , Cell Proliferation , Female , Humans , Middle AgedABSTRACT
Tumor-associated macrophage (TAM) is major component of tumor immune related inflammation and plays a crucial role in tumor immune escape. However, there have been no studies reported the relationship of TAM and immunosuppressive cell regulatory T cell (Treg) in NPC. This study is to discuss the interaction of TAM and Treg in NPC. In the present study, immunopathological assays demonstrated that M2 macrophage increased in NPC tissues. M2 macrophage had a positive correlation with aberrantly increased Foxp3+ Treg in NPC tissues. High density M2 macrophage and high density Treg predicted poor survival of NPC patients. In vitro studies using tumor cells co-cultured with monocyte indicated that tumor cells could induce monoctye into M2 macrophage via TGF-ß1 and IL-10. Tumor cells induced-M2 macrophage could induce the chemotaxis of Treg and increased the percent of Treg in PBMC. Our results proved that NPC cells induced M2 macrophage via TGF-ß1 and IL-10, and tumor cells induced-M2 macrophage could favor accumulation of Treg by conversion and chemotaxis.
ABSTRACT
Most of the world's natural fiber comes from cotton (Gossypium spp.), which is an important crop worldwide. Characterizing genes that regulate cotton yield and fiber quality is expected to benefit the sustainable production of natural fiber. Although a huge number of expressed sequence tag sequences are now available in the public database, large-scale gene function analysis has been hampered by the low-efficiency process of generating transgenic cotton plants. Tobacco rattle virus (TRV) has recently been reported to trigger virus-induced gene silencing (VIGS) in cotton leaves. Here, we extended the utility of this method by showing that TRV-VIGS can operate in reproductive organs as well. We used this method to investigate the function of KATANIN and WRINKLED1 in cotton plant development. Cotton plants with suppressed KATANIN expression produced shorter fibers and elevated weight ratio of seed oil to endosperm. By contrast, silencing of WRINKLED1 expression resulted in increased fiber length but reduced oil seed content, suggesting the possibility to increase fiber length by repartitioning carbon flow. Our results provide evidence that the TRV-VIGS system can be used for rapid functional analysis of genes involved in cotton fiber development.
