Requirement of endogenous stem cell factor and granulocyte-colony-stimulating factor for IL-17-mediated granulopoiesis

IL-17 is a novel, CD4(+) T cell-restricted cytokine. In vivo, it stimulates hematopoiesis and causes neutrophilia consisting of mature granulocytes. I n this study, we show that IL-17-mediated granulopoiesis requires G-CSF rel ease and the presence or induction of the transmembrane form of stem cell f actor (SCF) for optimal granulopoiesis. However, IL-17 also protects mice f rom G-CSF neutralization-induced neutropenia, G-CSF neutralization complete ly reversed IL-17-induced BM progenitor expansion, whereas splenic CFU-GM/C FU-granulocyte-erythrocyte-megakaryocyte-monocyte was only reduced by 50% i n both Sl/Sld and littermate control mice. Thus, there remained a significa nt SCF/G-CSF-independent effect of IL-17 on splenic granulopoiesis, resulti ng in a preservation of mature circulating granulocytes. IL-17 is a cytokin e that potentially interconnects lymphocytic and myeloid host defense and m ay have potential for therapeutic development.