Ruishi Zhang1, Yan-Nan Song2, Xiaoyan Duo1, Zhihong Guo3, Yanhua Sun4, Zhixiong Zhang4, Yongtian Lu5, Beiping Miao6, Ping-Chang Yang7,8, Guohui Nie9. 1. Department of Ophthalmology, Shenzhen Secondary Hospital and First Affiliated Hospital of Shenzhen University, Shenzhen, China. 2. Research Center of Allergy and Immunology, Shenzhen University School of Medicine, Room A7-509, Lihu Campus, 1066 Xueyuan Blvd, Shenzhen, 518055, China. 3. Shenzhen Luohu Medical Group, Shenzhen, China. 4. Department of Pathology, Shenzhen Secondary Hospital and First Affiliated Hospital of Shenzhen University, Shenzhen, China. 5. Department of Otolaryngology, Head and Neck Surgery, Shenzhen Secondary Hospital and First Affiliated Hospital of Shenzhen University, Shenzhen, China. 6. Department of Otolaryngology, Head and Neck Surgery, Shenzhen Secondary Hospital and First Affiliated Hospital of Shenzhen University, Shenzhen, China. miaobeiping@163.com. 7. Research Center of Allergy and Immunology, Shenzhen University School of Medicine, Room A7-509, Lihu Campus, 1066 Xueyuan Blvd, Shenzhen, 518055, China. pcy2356@szu.edu.cn. 8. Guangdong Provincial Key Laboratory of Regional Immunity and Diseases, Shenzhen, China. pcy2356@szu.edu.cn. 9. Department of Otolaryngology, Head and Neck Surgery, Shenzhen Secondary Hospital and First Affiliated Hospital of Shenzhen University, Shenzhen, China. nghui@21cn.com.
Abstract
BACKGROUND: The development of tumor tissue-infiltrating regulatory T cell (Treg) is incompletely understood. This study investigates the role of retinoblastoma cell (Rbc)-derived Twist‑related protein 1 (Twist) in the Treg development. METHODS: The surgically removed Rb tissues were collected. Rbcs were cultured with CD4+ T cells to assess the role of Rbc-derived Twist in the Treg generation. RESULTS: We found that more than 90% Rbcs expressed Twist. Foxp3+ Tregs were detected in the Rb tissues that were positively correlated with the Twist expression in Rbcs, negatively associated with Rb patient survival and sight survival. Treating Rbcs with hypoxia promoted the Twist expression that could be detected in the cytoplasm, nuclei and on the cell surface. Twist activated CD4+ T cells by binding the TLR4/myeloid differentiation factor 2 complex and promoted the transforming growth factor-β-inducible early gene 1 product and Foxp3 expression. These Rbc-induced Foxp3+ Tregs showed immune-suppressive function on CD8+ T cell proliferation. CONCLUSIONS: Rbcs express Twist, that induces IL-4+ Foxp3+ Tregs; the latter can inhibit CD8+ cytotoxic T cell activities. Therefore, Twist may play an important role in the pathogenesis of Rb.
BACKGROUND: The development of tumor tissue-infiltrating regulatory T cell (Treg) is incompletely understood. This study investigates the role of retinoblastoma cell (Rbc)-derived Twist‑related protein 1 (Twist) in the Treg development. METHODS: The surgically removed Rb tissues were collected. Rbcs were cultured with CD4+ T cells to assess the role of Rbc-derived Twist in the Treg generation. RESULTS: We found that more than 90% Rbcs expressed Twist. Foxp3+ Tregs were detected in the Rb tissues that were positively correlated with the Twist expression in Rbcs, negatively associated with Rb patient survival and sight survival. Treating Rbcs with hypoxia promoted the Twist expression that could be detected in the cytoplasm, nuclei and on the cell surface. Twist activated CD4+ T cells by binding the TLR4/myeloid differentiation factor 2 complex and promoted the transforming growth factor-β-inducible early gene 1 product and Foxp3 expression. These Rbc-induced Foxp3+ Tregs showed immune-suppressive function on CD8+ T cell proliferation. CONCLUSIONS: Rbcs express Twist, that induces IL-4+ Foxp3+ Tregs; the latter can inhibit CD8+ cytotoxic T cell activities. Therefore, Twist may play an important role in the pathogenesis of Rb.
Entities:
Keywords:
Apoptosis; Regulatory T cell; Retinoblastoma; Tumor tolerance; Twist
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