首页 / 院系成果 / 成果详情页

Obese donor mice splenocytes aggravated the pathogenesis of acute graft-versus-host disease via regulating differentiation of Tregs and CD4(+) T cell induced-type I inflammation 期刊论文

编号：

4cb74c3a-2a0c-4355-8a0f-7262fd7764f9
作者：

Li, Zengyao#^[1]Gu, Jian(古鉴)#^[1]Zhu, Qin(朱勤)#^[1]Liu, Jing^[2];Lu, Hao(鲁皓)^[1]Lu, Yunjie(陆云杰)^[1]Wang, Xuehao(王学浩)*^[1]
语种：

英文
期刊：

ONCOTARGET ISSN：1949-2553 2017 年 8 卷 43 期 (74880 - 74896) ; SEP 26
收录：
关键词：

obesity aGVHD transplantation
摘要：

Acute graft-versus-host disease (aGVHD) remains one of the most severe complications in organ and bone marrow transplantation, leading to much morbidity and mortality. Obesity has been associated with increased risk of development of various inflammatory diseases. Here, we investigated the in vitro and in vivo effects of obese donor splenocytes on the development of acute graft-versus-host disease (aGVHD). In this study, mixed lymphocyte reactions (MLR) in vitro showed that obese donor mouse CD4(+) T cell promoted the production of interleukin-2 (IL-2), interferon (IFN)-gamma and tumor necrosis factor (TNF)-alpha. Meanwhile, the inducible Tregs population decreased greatly in obese donor mouse CD4(+) T cells' induction group, compared with normal group. Then in the murine aGVHD model, we found that obese donor splenocytes dramatically increased the severity of aGVHD through down-regulating immune tolerance while enhancing systemic and local immunity. Moreover, we showed that aGVHD induced by obese donors resulted in massive expansion of donor CD3(+) T cells, release of Th1-related cytokines, interleukin-17 (IL-17) and chemokines, significant increase of Th17 cells and inhibition of CD4(+) CD25(+) Foxp3(+) regulatory T cells (Tregs) and impaired suppressive ability of donor Tregs. Expression of sphingosine- 1-phosphate receptor 1 (S1PR1), phosphorylated Akt, mammalian target of rapamycin (mTOR) and Raptor increased, while the phosphorylation level of SMAD3 was decreased in the skin, intestine, lung and liver from obese donor splenocytes-treated aGVHD mice. Furthermore, at mRNA and protein levels, we defined several molecules that may account for the enhanced ability of obese donor splenocytes to migrate into target organs, such as IL-2, IL-17, IFN-gamma, TNF-alpha, CXCR3, CXCL9, CXCL10, CXCL11 and CCL3. Therefore, these results imply that obese donor cells may be related to the risk of aGVHD and helping obese donor individuals lose weight represent a compulsory clinical strategy before implementing transplantation to control aGVHD of recipients.
推荐引用方式
GB/T 7714：

Li Zengyao,Gu Jian,Zhu Qin, et al. Obese donor mice splenocytes aggravated the pathogenesis of acute graft-versus-host disease via regulating differentiation of Tregs and CD4(+) T cell induced-type I inflammation [J].ONCOTARGET,2017,8(43):74880-74896.
APA：

Li Zengyao,Gu Jian,Zhu Qin,Liu Jing,&Wang Xuehao.(2017).Obese donor mice splenocytes aggravated the pathogenesis of acute graft-versus-host disease via regulating differentiation of Tregs and CD4(+) T cell induced-type I inflammation .ONCOTARGET,8(43):74880-74896.
MLA：

Li Zengyao, et al. "Obese donor mice splenocytes aggravated the pathogenesis of acute graft-versus-host disease via regulating differentiation of Tregs and CD4(+) T cell induced-type I inflammation" .ONCOTARGET 8,43(2017):74880-74896.
入库时间：

9/29/2019 6:18:07 PM
更新时间：

9/29/2019 6:18:07 PM
条目包含文件：

文件类型： , 文件大小：

正在加载全文

未找到全文

浏览次数：46  下载次数：0

分享到：

浏览次数：46

下载次数：0

打印次数：0