Regulation of neutrophil homeostasis by IL-17A and IL-17F-producing gamma-delta-T-cells

中性粒细胞是人类最丰富的白细胞，在先天免疫中至关重要，但也具有重要的破坏性潜力。因此，它们的数量必须得到严格控制。最近研究表明，T细胞通过分泌促炎细胞因子白介素17(IL-17)来调节中性粒细胞数量，从而产生G-CSF。T细胞产生IL-17家族的两个成员，IL-17A和IL-17F。初步数据显示，虽然IL-17受体缺陷会导致中性粒细胞减少，但IL-17A缺陷不会。因此，我将测试IL-17F是否可以作为一种替代的细胞因子来调节粒细胞生成。初步数据表明，主要的中性粒细胞调节性T细胞亚群是T细胞。我将研究T细胞对IL-17诱导的细胞因子IL-23的反应。抗T细胞免疫抑制剂霉酚酸(MPA)可引起中性粒细胞减少，其机制不明。我将评估甲孕酮对中性粒细胞调节性T细胞的影响。更好地了解T细胞如何调节中性粒细胞的动态平衡有助于改进免疫抑制方案和中性粒细胞减少症的治疗。

Neutrophilic granulocytes, the most abundant human white blood cells, are critical in innate immunity, but also have an important destructive potential. Thus, their numbers must be tightly controlled. T-cells have recently been shown to regulate neutrophil numbers through secretion of the proinflammatory cytokine Interleukin (IL)-17, which induces G-CSF. T-cells produce two members of the IL-17 family, IL-17A and IL-17F. Preliminary data show that while IL-17 receptor deficiency results in neutropenia, IL-17Adeficiency does not. Thus, I will test if IL-17F can be an alternative cytokine in regulation of granulopoiesis. Preliminary data suggest that the main neutrophil regulatory T-cell subset is T-cells. I will study the response of T-cells to the IL-17-inducing cytokine IL-23. The anti-T-cell immunosuppressant mycophenolic acid (MPA) can cause neutropenia by an unknown mechanism. I will assess the effect of MPA on neutrophil regulatory T-cells. A better understanding of how T-cells regulate neutrophil homeostasis could aid in improving immunosuppressive regimens and treatment of neutropenia.