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

嗜中性粒细胞是人类最丰富的白色血细胞，在先天免疫中至关重要，但也具有重要的破坏潜力。因此，必须严格控制其数量。最近已经显示T细胞通过分泌促炎细胞因子白细胞介素（IL）-17（其诱导G-CSF）来调节中性粒细胞数目。T细胞产生IL-17家族的两个成员，IL-17 A和IL-17 F。初步数据显示，虽然IL-17受体缺乏导致中性粒细胞减少，但IL-17 A缺乏不会。因此，我将测试IL-17 F是否可以作为调节粒细胞生成的替代细胞因子。初步数据表明，主要的中性粒细胞调节性T细胞亚群是嗜中性粒细胞T细胞。我将研究血小板T细胞对IL-17诱导细胞因子IL-23的反应。抗T细胞免疫抑制剂麦考酚酸（MPA）可引起中性粒细胞减少，其机制尚不清楚。我将评估MPA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稳态有助于改善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.