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

产生 IL-17A 和 IL-17F 的 γ-δ T 细胞对中性粒细胞稳态的调节

• 批准号: 69487727
• 负责人: Professorin Dr. Sibylle von Vietinghoff
• 金额: --
• 依托单位: Medizinische Klinik und Poliklinik I - Allgemeine Innere Medizin
• 依托单位国家: 德国
• 项目类别: Research Fellowships
• 财政年份: 2008
• 资助国家: 德国
• 起止时间: 2007-12-31 至 2009-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/69487727?language=en
• 关键词: Regulation; neutrophil; homeostasis; IL; 17A

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.

中性粒细胞是最丰富的人类白细胞，在先天免疫中至关重要，但也具有重要的破坏性潜力。因此，他们的数量必须严格控制。t细胞最近被证明通过分泌促炎细胞因子白介素(IL)-17来调节中性粒细胞数量，IL -17可诱导G-CSF。t细胞产生两种IL-17家族成员，IL-17A和IL-17F。初步数据显示，IL-17受体缺乏会导致中性粒细胞减少症，而il - 17a缺乏则不会。因此，我将测试IL-17F是否可以作为调节颗粒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t细胞。我将研究t细胞对il -17诱导细胞因子IL-23的反应。抗t细胞免疫抑制剂霉酚酸（MPA）可引起中性粒细胞减少症，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治疗中性粒细胞减少症。