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Requirement of Endogenous Stem Cell Factor and Granulocyte-Colony-Stimulating Factor for IL-17-Mediated Granulopoiesis¹

Paul Schwarzenberger^2,*,, Weitao Huang^*,, Peng Ye^*,, Peter Oliver^*,, Misty Manuel^*,, Zili Zhang^*,,, Gregory Bagby^§, Steve Nelson and Jay K. Kolls^*,,

^* Gene Therapy Program and Departments of Medicine, Pediatrics, and ^§ Physiology, Louisiana State University Health Science Center, New Orleans, LA70112

IL-17 is a novel, CD4⁺ T cell-restricted cytokine. In vivo, it stimulates hematopoiesis and causes neutrophilia consisting of mature granulocytes. In this study, we show that IL-17-mediated granulopoiesis requires G-CSF release and the presence or induction of the transmembrane form of stem cell factor (SCF) for optimal granulopoiesis. However, IL-17 also protects mice from G-CSF neutralization-induced neutropenia. G-CSF neutralization completely reversed IL-17-induced BM progenitor expansion, whereas splenic CFU-GM/CFU-granulocyte-erythrocyte-megakaryocyte-monocyte was only reduced by 50% in both Sl/Sld and littermate control mice. Thus, there remained a significant SCF/G-CSF-independent effect of IL-17 on splenic granulopoiesis, resulting in a preservation of mature circulating granulocytes. IL-17 is a cytokine that potentially interconnects lymphocytic and myeloid host defense and may have potential for therapeutic development.