EA4273 Biometadys, Faculté de Médecine, Université de Nantes, Nantes, France.
Leukemia. 2012 Jul;26(7):1471-4. doi: 10.1038/leu.2012.41. Epub 2012 Feb 15.
The contribution of Th17 cells in acute graft-versus-host disease (aGVHD) has been demonstrated in aGVHD mouse models. However, their contribution in human gastrointestinal aGVHD remains unclear. We evaluated Th17 cells in a cohort of 23 patients at diagnosis of aGVHD. In this study, we have shown that the absolute number of Th17 cells using the CCR6 and CD161 markers were significantly higher in the intestinal mucosa of patients with aGVHD compared with intestinal mucosa of patients without aGVHD. Moreover, in keeping with the increase of CCR6+ and CD161+ T cells, RORγt the key transcription factor that orchestrates the differentiation of Th17 cells, was significantly increased in the intestinal mucosa of patients with aGVHD compared with intestinal mucosa of patients without aGVHD (P=0.01). Since plasmacytoid dendritic cells (PDCs) have been reported to drive the differentiation of the Th17 subset, we quantified PDCs in these patients. PDC CD123+ cells were increased in the intestinal mucosa of patients with aGVHD. Furthermore, the number of CD123+ PDCs paralleled the histological grade of aGVHD, providing evidence for a role of Th17-mediated responses and a potential new pathophysiological link between PDCs and Th17 in human aGVHD.
Th17 细胞在急性移植物抗宿主病（aGVHD）中的作用在 aGVHD 小鼠模型中得到了证实。然而，其在人类胃肠道 aGVHD 中的作用尚不清楚。我们在 23 例 aGVHD 患者的队列中评估了 Th17 细胞。在这项研究中，我们表明，与无 aGVHD 的患者的肠黏膜相比，aGVHD 患者的肠黏膜中使用 CCR6 和 CD161 标志物的 Th17 细胞的绝对数量显著更高。此外，与 CCR6+和 CD161+T 细胞的增加一致，RORγt，协调 Th17 细胞分化的关键转录因子，在 aGVHD 患者的肠黏膜中与无 aGVHD 的患者相比显著增加（P=0.01）。由于已报道浆细胞样树突状细胞（PDCs）可驱动 Th17 亚群的分化，我们在这些患者中定量了 PDCs。aGVHD 患者的肠黏膜中 PDC CD123+细胞增加。此外，CD123+PDC 的数量与 aGVHD 的组织学分级平行，为 Th17 介导的反应以及 PDCs 和 Th17 在人类 aGVHD 中的潜在新的病理生理学联系提供了证据。
