Journal
JOURNAL OF IMMUNOLOGY
Volume 181, Issue 2, Pages 1357-1364Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.181.2.1357
Keywords
-
Categories
Funding
- NHLBI NIH HHS [HL73361, P01 HL073361-03, P01 HL073361, P01 HL073361-02, P01 HL073361-05, P01 HL073361-01A1, P01 HL073361-04] Funding Source: Medline
- NIGMS NIH HHS [T32 GM008715, T32 GM 08715-01A1] Funding Source: Medline
Ask authors/readers for more resources
IL-23 and IL-17A regulate granulopoiesis through G-CSF, the main granulopoietic cytokine. IL-23 is secreted by activated macrophages and dendritic calls and promotes the expansion of three subsets of IL-17A-expressing neutrophil-regulatory T (Tn) cells; CD4(-)CD8(-)alpha beta(low), CD4(+)CD8(-)alpha beta(+) (Th17), and gamma delta(+) 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 beta(2) 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 1l17ra(-/-) 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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available