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

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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.