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. 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.
Schwarzenberger
P
P
Gene Therapy Program and Departments of Medicine, Pediatrics, and Physiology, Louisiana State University Health Science Center, New Orleans, LA 70112, USA. pschwa1@lsumc.edu
Huang
W
W
Ye
P
P
Oliver
P
P
Manuel
M
M
Zhang
Z
Z
Bagby
G
G
Nelson
S
S
Kolls
J K
JK
D016475:3T3 Cells; D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D001854:Bone Marrow Cells / Q000378:metabolism; D002455:Cell Division / Q000276:immunology; D002460:Cell Line; D003114:Colony-Forming Units Assay; D004357:Drug Synergism; D018014:Gene Transfer Techniques; D016179:Granulocyte Colony-Stimulating Factor / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology*; D006098:Granulocytes / Q000166:cytology* / Q000276:immunology; D006411:Hematopoiesis, Extramedullary / Q000235:genetics / Q000276:immunology; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000276:immunology; D007275:Injections, Intravenous; D020381:Interleukin-17 / Q000008:administration & dosage / Q000235:genetics / Q000502:physiology*; D019891:Leukopoiesis / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008817:Mice, Mutant Strains; D013154:Spleen / Q000166:cytology / Q000276:immunology; D019089:Stem Cell Factor / Q000096:biosynthesis / Q000502:physiology*; D017154:Stromal Cells / Q000378:metabolism
D020381:Interleukin-17; D019089:Stem Cell Factor; D016179:Granulocyte Colony-Stimulating Factor