Phagocytosis of Apoptotic Neutrophils Regulates Granulopoiesis via IL-23 and IL-17

Homeostatic regulation of neutrophil production is thought to match neutrophil elimination to maintain approximately constant numbers in the blood. Here, we show that IL-17, a cytokine that regulates granulopoiesis through G-CSF, is made by γδ T cells and unconventional αβ T cells. These neutrophil-...

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Bibliographic Details
Published in:Immunity (Cambridge, Mass.) Mass.), 2005-03, Vol.22 (3), p.285-294
Main Authors: Stark, Matthew A., Huo, Yuqing, Burcin, Tracy L., Morris, Margaret A., Olson, Timothy S., Ley, Klaus
Format: Article
Language:English
Subjects:
Adoptive Transfer
Animals
Apoptosis
Apoptosis - immunology
Bone Marrow - immunology
CD18 Antigens - immunology
CD18 Antigens - metabolism
Cell Adhesion Molecules - deficiency
Cell Transplantation
Chemotaxis, Leukocyte - immunology
Colleges & universities
Cytokines
Dendritic Cells - immunology
Granulocytes - immunology
Homeostasis
Hypotheses
Interleukin-17 - immunology
Interleukin-17 - metabolism
Interleukin-23
Interleukin-23 Subunit p19
Interleukins - immunology
Interleukins - metabolism
Leukocytes
Lymphocytes
Macrophages - immunology
Medicine
Mice
Mice, Knockout
Neutrophils - immunology
Neutrophils - metabolism
Neutrophils - pathology
Phagocytosis - immunology
Reverse Transcriptase Polymerase Chain Reaction
RNA, Messenger - analysis
Rodents
Spleen
T cell receptors
T-Lymphocytes - immunology
T-Lymphocytes - metabolism
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Summary:Homeostatic regulation of neutrophil production is thought to match neutrophil elimination to maintain approximately constant numbers in the blood. Here, we show that IL-17, a cytokine that regulates granulopoiesis through G-CSF, is made by γδ T cells and unconventional αβ T cells. These neutrophil-regulatory T cells (Tn) are expanded in mice that lack leukocyte adhesion molecules, which have neutrophilia and defective neutrophil trafficking. Normal neutrophils migrate to tissues, where they become apoptotic and are phagocytosed by macrophages and dendritic cells. This curbs phagocyte secretion of IL-23, a cytokine controlling IL-17 production by Tn cells. Adoptive transfer of wild-type, but not adhesion molecule-deficient, neutrophils into mice deficient in β 2 integrins transiently decreases neutrophilia and reduces levels of serum IL-17. Antibody blockade of the p40 subunit of IL-23 reduces neutrophil numbers in wild-type mice. These findings identify a major homeostatic mechanism for the regulation of neutrophil production in vivo.
ISSN:1074-7613
1097-4180
DOI:10.1016/j.immuni.2005.01.011