J Clin Invest. 2014 Feb;124(2):543-52. doi: 10.1172/JCI71858. Epub 2014 Jan 27.
Th cells are the major effector cells in transplant rejection and can be divided into Th1, Th2, Th17, and Treg subsets. Th differentiation is controlled by transcription factor expression, which is driven by positive and negative cytokine and chemokine stimuli at the time of T cell activation. Here we discovered that chemokine platelet factor 4 (PF4) is a negative regulator of Th17 differentiation. PF4-deficient and platelet-deficient mice had exaggerated immune responses to cardiac transplantation, including increased numbers of infiltrating Th17 cells and increased plasma IL-17. Although PF4 has been described as a platelet-specific molecule, we found that activated T cells also express PF4. Furthermore, bone marrow transplantation experiments revealed that T cell-derived PF4 contributes to a restriction in Th17 differentiation. Taken together, the results of this study demonstrate that PF4 is a key regulator of Th cell development that is necessary to limit Th17 differentiation. These data likely will impact our understanding of platelet-dependent regulation of T cell development, which is important in many diseases, in addition to transplantation.
Th 细胞是移植排斥反应的主要效应细胞，可分为 Th1、Th2、Th17 和 Treg 亚群。Th 细胞的分化受转录因子表达的控制，而转录因子的表达又受到 T 细胞激活时阳性和阴性细胞因子和趋化因子刺激的驱动。在这里，我们发现趋化因子血小板因子 4（PF4）是 Th17 分化的负调节剂。PF4 缺陷和血小板缺陷小鼠对心脏移植的免疫反应过度，包括浸润的 Th17 细胞数量增加和血浆 IL-17 增加。尽管 PF4 已被描述为血小板特异性分子，但我们发现活化的 T 细胞也表达 PF4。此外，骨髓移植实验表明，T 细胞衍生的 PF4 有助于限制 Th17 分化。总之，这项研究的结果表明，PF4 是 Th 细胞发育的关键调节剂，对于限制 Th17 分化是必要的。这些数据可能会影响我们对血小板依赖性 T 细胞发育调节的理解，除了移植之外，这在许多疾病中也很重要。
