PD-L1 Ameliorates Murine Acute Graft-Versus-Host Disease by Suppressing Effector But Not Regulatory T Cells Function
PD-L1 Ameliorates Murine Acute Graft-Versus-Host Disease by Suppressing Effector But Not Regulatory T Cells Function
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PD-L1 通过抑制效应细胞而非调节性 T 细胞功能来改善小鼠急性移植物抗宿主病
DOI：
10.1007/s00005-019-00539-4
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发表时间：
2019-03
影响因子：
3.2
通讯作者：
Sun Aining
中科院分区：
文献类型：
--
作者：
Tang Lin;Ma Shoubao;Gong Huanle;Wang Jun;Xu Yang;Wu Depei;Sun Aining
越来越多的证据表明程序性死亡 1 (PD-1) 及其配体 PD-1 (PD-L1) 之间的相互作用在急性移植物抗宿主病 (aGVHD) 的病理学中发挥着关键作用。然而，PD-L1在aGVHD发展中的作用在最近的小鼠研究中一直存在争议。在本研究中，我们在小鼠 aGVHD 模型中进行了研究，以阐明 PD-L1 在 aGVHD 发病机制中的作用。我们发现通过体内水动力基因转移（HGT）方法全身性过度表达PD-L1可改善aGVHD诱导的小鼠致死率。 PD-L1 的全身过度表达会抑制供体 T 细胞的激活、效应记忆状态以及体内 Th1 和 Th17 细胞的反应。此外，PD-L1 Ig 治疗在体外刺激抗 CD3/CD28 和同种异体树突状细胞时，显着抑制 T 细胞增殖，促进 T 细胞凋亡，并减少效应 T 细胞促炎细胞因子的表达。然而，我们发现PD-L1过表达并不影响Treg细胞在体内和体外的分化，PD-L1 HGT受体中Treg细胞的耗竭并没有加重aGVHD死亡率。因此，我们的结果表明，PD-L1 蛋白的全身治疗通过抑制效应而非调节性 T 细胞功能来改善 aGVHD。我们的研究结果表明，PD-L1 全身治疗可能是预防或改善 aGVHD 的潜在策略。
There is increasing evidence that interaction between programmed death 1 (PD-1) and its ligands PD-1 (PD-L1) plays a critical role in the pathology of acute graft-versus-host disease (aGVHD). However, the role of PD-L1 in the development of aGVHD has been controversial in recent mouse studies. In this study, we carried out studies in a murine aGVHD model to clarify the role of PD-L1 in aGVHD pathogenesis. We found that systemic overexpression of PD-L1 by hydrodynamic gene transfer (HGT) method in vivo ameliorates aGVHD-induced lethality in mice. Systemic overexpression of PD-L1 inhibits the donor T cells activation, effector memory status, as well as Th1 and Th17 cells responses in vivo. In addition, PD-L1 Ig treatment significantly suppressed T cells’ proliferation, promoted T cells’ apoptosis, and reduced pro-inflammatory cytokines expression by effector T cells in vitro in the stimulation of anti-CD3/CD28 and allogeneic dendritic cells. However, we found that PD-L1 overexpression did not affect Treg cells’ differentiation in vivo and in vitro, depletion of Treg cells in PD-L1 HGT recipients did not aggravate aGVHD mortality. Therefore, our results demonstrated that systemic treatment with PD-L1 protein ameliorates aGVHD by suppressing effector but not regulatory T cell function. Our findings suggest that systemic treatment with PD-L1 may be a potential strategy to prevent or ameliorate aGVHD.
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B7H1/CD80 相互作用增强 PD-1 依赖性 T 细胞凋亡并改善移植物抗宿主病
DOI：
10.4049/jimmunol.1402157
发表时间：
2015-01-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Deng R;Cassady K;Li X;Yao S;Zhang M;Racine J;Lin J;Chen L;Zeng D
通讯作者：
Zeng D
影响因子：
7.3
作者：
Ghimire S;Weber D;Mavin E;Wang XN;Dickinson AM;Holler E
通讯作者：
Holler E
影响因子：
15.9
作者：
Saha, Asim;O'Connor, Roddy S.;Blazer, Bruce R.
通讯作者：
Blazer, Bruce R.
影响因子：
4.4
作者：
Blazar, BR;Carreno, BM;Taylor, PA
通讯作者：
Taylor, PA
影响因子：
3.5
作者：
Santos, Nazly;Rodriguez-Romanos, Rocio;Gallardo, David
通讯作者：
Gallardo, David