title: Protection of acute GVHD by all-trans retinoic acid through suppression of T cell expansion and induction of regulatory T cells through IL-2 signaling.
abstract: All-trans retinoic acid (atRA), the active derivative of vitamin A, has been shown to regulate Treg and T effector cell differentiation. However, the potential use of atRA as a treatment for acute graft-verse-host disease (aGVHD) has not been realized. Here we studied the ability of atRA to prevent and treat acute-GVHD in the B6-to-F1(D2B6F1) murine model. Our results showed that atRA consistently displayed a potent ability to control aGVHD development and reduce mortality by suppressing the expansion of donor T cells and inhibiting cytokine expression from donor CD8 cells. Interestingly, CD4(+)Foxp3(+) regulatory T cells were markedly increased in the spleens of atRA-treated mice. In vitro treatment with atRA inhibited T cell proliferation in a dose-dependent manner. Injection of an anti-IL-2 antibody impaired the protection by atRA in aGVHD. Therefore, these results strongly implicate atRA as a novel therapeutic strategy for controlling aGVHD progression and treating other inflammatory diseases.
authors: Changzhou No. 2 People's Hospital, Affiliated Hospital of Nanjing Medical University, Changzhou, 213003, China.
authors: Haojun
authors: H
authors: Yang
authors: Translational Medicine Research Center of Jiangning Hospital, Nanjing Medical University and Liver Transplantation Center of First Affiliated Hospital, Nanjing, China.
authors: Jian
authors: J
authors: Gu
authors: Translational Medicine Research Center of Jiangning Hospital, Nanjing Medical University and Liver Transplantation Center of First Affiliated Hospital, Nanjing, China.
authors: Qin
authors: Q
authors: Zhu
authors: Translational Medicine Research Center of Jiangning Hospital, Nanjing Medical University and Liver Transplantation Center of First Affiliated Hospital, Nanjing, China.
authors: Hao
authors: H
authors: Lu
authors: Translational Medicine Research Center of Jiangning Hospital, Nanjing Medical University and Liver Transplantation Center of First Affiliated Hospital, Nanjing, China.
authors: Kunpeng
authors: K
authors: Wang
authors: Translational Medicine Research Center of Jiangning Hospital, Nanjing Medical University and Liver Transplantation Center of First Affiliated Hospital, Nanjing, China.
authors: Xuhao
authors: X
authors: Ni
authors: Translational Medicine Research Center of Jiangning Hospital, Nanjing Medical University and Liver Transplantation Center of First Affiliated Hospital, Nanjing, China.
authors: Yunjie
authors: Y
authors: Lu
authors: Translational Medicine Research Center of Jiangning Hospital, Nanjing Medical University and Liver Transplantation Center of First Affiliated Hospital, Nanjing, China. Electronic address: lvling@njmu.edu.cn.
authors: Ling
authors: L
authors: Lu
mesh_terms: D000818:Animals; D016207:Cytokines / Q000276:immunology*; D006086:Graft vs Host Disease / Q000188:drug therapy / Q000276:immunology*; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D015398:Signal Transduction / Q000187:drug effects; D013154:Spleen / Q000187:drug effects / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000276:immunology; D014212:Tretinoin / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D016207:Cytokines; D014212:Tretinoin
keywords: GVHD; IL-2; atRA