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

• Applicant: Professorin Dr. Sibylle von Vietinghoff
• Subject Area: Nephrology
• Term: from 2008 to 2010
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 69487727

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.

• DFG Programme: Research Fellowships
• International Connection: USA
• Host: Professor Dr. Klaus Ley