State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Disease Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China.
Department of Hematology, Affiliated Suzhou Hospital of Nanjing Medical University (Suzhou Municipal Hospital), Suzhou, China.
Clin Exp Immunol. 2019 Mar;195(3):345-357. doi: 10.1111/cei.13233. Epub 2018 Nov 25.
Current researches have determined the significance of C-C chemokine receptor (CCR)6 expression as either a marker of T helper cells (Th) or an effector and regulator of T cell function. However, the roles of CCR6 in the pathogenesis of immune thrombocytopenia (ITP) are unclear. In this study, we aimed to investigate the phenotype and functional characteristics of circulating CCR6 T cells in blood from chronic ITP patients and healthy controls. We found that the frequency of CCR6 CD4 cells was higher in ITP patients than in healthy controls. Anti-CD3/anti-CD28 stimulation induced rapid expansion of CCR6 CD4 cells in ITP patients. CCR6 CD4 cells had a phenotype of activated cells and predominantly expressed CD45RO. Forkhead box protein P3 (FoxP3) and CD25-positive cells were exclusively detected within the CCR6 CD4 cells. In ITP patients, CCR6 regulatory T cells (T ) were decreased and positively correlated with platelet counts and transforming growth factor (TGF)-β plasma levels. In contrast to CCR6 counterparts, CCR6 CD4 cells produced higher levels of interleukin (IL)-17A. The frequency of CCR6 Th17 was higher in ITP patients and positively correlated with IL-17A levels in supernatant. Most importantly, CCR6 CD4 cell subpopulations, but not CCR6 CD4 , were closely correlated to treatment response of ITP patients. These findings suggest that circulating CCR6 CD4 cells in ITP patients have characteristics of activated memory Th17 phenotype and could be used to monitor disease activity and treatment response.
目前的研究已经确定了 C-C 趋化因子受体 (CCR)6 表达作为辅助性 T 细胞 (Th) 标志物或 T 细胞功能的效应物和调节剂的意义。然而，CCR6 在免疫性血小板减少症 (ITP) 发病机制中的作用尚不清楚。在本研究中，我们旨在研究慢性 ITP 患者和健康对照者外周血循环 CCR6 T 细胞的表型和功能特征。我们发现，ITP 患者 CCR6 CD4 细胞的频率高于健康对照组。抗 CD3/抗 CD28 刺激可诱导 ITP 患者 CCR6 CD4 细胞快速扩增。CCR6 CD4 细胞表现出激活细胞的表型，主要表达 CD45RO。FoxP3 和 CD25 阳性细胞仅存在于 CCR6 CD4 细胞中。在 ITP 患者中，CCR6 调节性 T 细胞 (Treg) 减少，并与血小板计数和转化生长因子 (TGF)-β 血浆水平呈正相关。与 CCR6 相比，CCR6 CD4 细胞产生更高水平的白细胞介素 (IL)-17A。ITP 患者 CCR6 Th17 的频率更高，与上清液中 IL-17A 水平呈正相关。最重要的是，CCR6 CD4 细胞亚群与 ITP 患者的治疗反应密切相关，但 CCR6 CD4 细胞亚群与治疗反应无关。这些发现表明，ITP 患者外周血循环 CCR6 CD4 细胞具有激活的记忆性 Th17 表型特征，可用于监测疾病活动和治疗反应。
