Attenuation of acute graft-versus-host disease in the absence of the transcription factor RORγt.
Attenuation of acute graft-versus-host disease in the absence of the transcription factor RORγt.
复制标题
DOI：
10.4049/jimmunol.1200858
复制
发表时间：
2012-08-15
期刊：
影响因子：
--
通讯作者：
Serody JS
中科院分区：
文献类型：
--
作者：
Fulton LM;Carlson MJ;Coghill JM;Ott LE;West ML;Panoskaltsis-Mortari A;Littman DR;Blazar BR;Serody JS
移植物抗宿主病（GvHD）仍然是异基因造血干细胞移植（allo-SCT）后最重要的并发症。以前，急性GvHD被认为主要由Th 1极化T细胞介导。最近，研究人员已经确定了第二个促炎T细胞谱系，称为Th 17，它严重依赖于转录因子RORγt。在这里，我们通过输注缺乏RORC的供体T细胞以及因此的同种型RORγt来评估Th 17细胞在小鼠急性GvHD中的作用。给予缺乏RORC的供体CD 4+和CD 8 + T细胞的受体显著减弱了急性GvHD，并显著降低了结肠、肝脏和肺的组织病理学。使用临床相关的单倍体相合小鼠移植模型，我们发现RORC−/− CD 4 + T细胞单独降低了aGvHD的严重性和致死性。当将来自RORC−/−小鼠的CD 4 + T细胞给予完全不匹配的BALB/c小鼠时，没有发现这一点，并且与移植后结肠中TNF产生的绝对差异相关。因此，RORC的CD 4 + T细胞表达在急性GVHD的发病机制中是重要的。
Graft-versus-host disease (GvHD) remains the most significant complication after allogeneic stem cell transplantation (allo-SCT). Previously, acute GvHD had been considered to be mediated predominantly by Th1 polarized T cells. Recently, investigators have identified a second pro-inflammatory lineage of T cells termed Th17 that is critically dependent on the transcription factor RORγt. Here, we have evaluated the role of Th17 cells in murine acute GvHD by infusing donor T cells lacking RORC and as a consequence the isoform RORγt. Recipients given donor CD4+ and CD8+ T cells lacking RORC had significantly attenuated acute GvHD and markedly decreased tissue pathology in the colon, liver, and lung. Using a clinically relevant haploidentical murine transplantation model, we showed that RORC−/− CD4+ T cells alone diminished the severity and lethality of aGvHD. This was not found when CD4+ T cells from RORC−/− mice were given to completely mismatched BALB/c mice, and correlated with absolute differences in the generation of TNF in the colon post transplant. Thus, CD4+ T cell expression of RORC is important in the pathogenesis of acute GVHD.
登录
查看更多内容
影响因子：
64.8
作者：
Bettelli, E;Carrier, YJ;Kuchroo, VK
通讯作者：
Kuchroo, VK
影响因子：
64.5
作者：
Ivanov, Ivaylo I.;McKenzie, Brent S.;Littman, Dan R.
通讯作者：
Littman, Dan R.
影响因子：
20.3
作者：
Beilhack, A;Schulz, S;Negrin, RS
通讯作者：
Negrin, RS
影响因子：
20.3
作者：
Blazar, BR;Taylor, PA;Vallera, DA
通讯作者：
Vallera, DA
影响因子：
13
作者：
Kolls, Jay K.;Khader, Shabaana A.
通讯作者：
Khader, Shabaana A.