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

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• 作者：Haojun Yang^a ; ¹ ; Jian Gu^b ; ¹ ; Qin Zhu^b ; Hao Lu^b ; Kunpeng Wang^b ; Xuhao Ni^b ; Yunjie Lu^b ; Ling Lu^b ; ^{lvling@njmu.edu.cn" class="auth_mail" title="E-mail the corresponding author}
• 关键词：aGVHD ; acute graft-verse-host disease ; Foxp3 ; forkhead box P3 ; Treg ; regulatory T cell ; nTreg ; natural regulatory T cell ; atRA ; all-trans retinoid acid ; TCR ; T cell receptor ; APC ; antigen presenting cell
• 刊名：International Immunopharmacology
• 出版年：2015
• 出版时间：October 2015
• 年：2015
• 卷：28
• 期：2
• 页码：911-916
• 全文大小：767 K

文摘

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.