IL-17A inhibits the expansion of IL-17A-producing T cells in mice through "short-loop" inhibition via IL-17 receptor

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

Research output: Contribution to journalArticlepeer-review

96 Scopus citations


IL-23 and IL-17A regulate granulopoiesis through G-CSF, the main granulopoietic cytokine. IL-23 is secreted by activated macrophages and dendritic cells and promotes the expansion of three subsets of IL-17A-expressing neutrophil-regulatory T (Tn) cells; CD4-CD8 -αβlow, CD4+CD8 -αβ+ (Th17), and γδ+ T cells. In this study, we investigate the effects of IL-17A on circulating neutrophil levels using IL-17R-deficient (Il17ra-/-) mice and Il17ra-/-Itgb2-/- mice that lack both IL-17R and all four β2 integrins. IL-17R deficiency conferred a reduction in neutrophil numbers and G-CSF levels, as did Ab blockade against IL-17A in wild-type mice. Bone marrow transplantation revealed that IL-17R expression on nonhemopoietic cells had the greatest effects on regulating blood neutrophil counts. Although circulating neutrophil numbers were reduced, IL-17A expression, secretion, and the number of IL-17A-producing Tn cells were elevated in Il17ra-/- and Il17ra-/-Itgb2-/- mice, suggesting a negative feedback effect through IL-17R. The negative regulation of IL-17A-producing T cells and IL-17A and IL-17F gene expression through the interactions of IL-17A or IL-17F with IL-17R was confirmed in splenocyte cultures in vitro. We conclude that IL-17A regulates blood neutrophil counts by inducing G-CSF production mainly in nonhemopoietic cells. IL-17A controls the expansion of IL-17A-producing Tn cell populations through IL-17R.

Original languageEnglish (US)
Pages (from-to)1357-1364
Number of pages8
JournalJournal of Immunology
Issue number2
StatePublished - Jul 15 2008
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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