Phagocytosis of apoptotic neutrophils regulates granulopoiesis via IL-23 and IL-17

Matthew A. Stark, Yuqing Huo, Tracy L. Burcin, Margaret A. Morris, Timothy S. Olson, Klaus Ley

Research output: Contribution to journalArticlepeer-review

649 Scopus citations

Abstract

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 β2 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.

Original languageEnglish (US)
Pages (from-to)285-294
Number of pages10
JournalImmunity
Volume22
Issue number3
DOIs
StatePublished - Mar 2005
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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