IL-23 is required for neutrophil homeostasis in normal and neutrophilic mice

Emily Smith, Alexander Zarbock, Matthew A. Stark, Tracy L. Burcin, Anthony C. Bruce, Patricia Foley, Klaus Ley

Research output: Contribution to journalArticlepeer-review

74 Scopus citations


IL-23 is secreted by macrophages and dendritic cells in response to microbial products and inflammatory cytokines. IL-23 is a heterodimer composed of the unique IL-23p19 subunit linked to the common p40 subunit that it shares with IL-12. IL-23 is implicated in autoimmune diseases, where it supports the expansion of IL-17A-producing CD4+ Th17 cells. IL-23 also regulates granulopoiesis in a neutrostat regulatory feedback loop through IL-17A-producing neutrophil regulatory (Tn) cells, most of which express γδ TCR. This homeostatic system is disrupted in mice lacking adhesion molecules like β2-integrins (Itgb2-/-) which have defective neutrophil trafficking and neutrophilia. To test the role of IL-23 in the homeostatic regulation of circulating neutrophil numbers, we measured blood neutrophil numbers in p40-deficient (IL12b-/-) mice and found them reduced compared with wild-type mice. IL12b-/-Itgb2-/- mice, lacking β2-integrins, IL-12, and IL-23 showed significantly blunted neutrophilia compared with Itgb2-/- mice. Treatment of both IL12b-/- and IL12b-/-Itgb2-/- mice with IL-23, but not IL-12, restored circulating neutrophil counts. Serum levels of IL-17A were readily detectable in Itgb2-/- mice, but not in IL12b-/-Itgb2-/- mice, suggesting that IL-17A production is reduced when IL-23 is absent. Similarly, tissue mRNA expression of IL-17A was reduced in IL12b-/-Itgb2-/- mice compared with Itgb2 -/- controls. The total number of CD3+ IL-17A-producing Tn cells were significantly reduced in the spleen and lamina propria of IL12b -/-Itgb2-/- mice, with the largest reduction found in γδ+ T cells. Our results suggest a prominent role of IL-23 in the regulation of granulopoiesis and the prevalence of IL-17A-producing Tn cells.

Original languageEnglish (US)
Pages (from-to)8274-8279
Number of pages6
JournalJournal of Immunology
Issue number12
StatePublished - Dec 15 2007
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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