2007
DOI: 10.4049/jimmunol.179.12.8274
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IL-23 Is Required for Neutrophil Homeostasis in Normal and Neutrophilic Mice

Abstract: 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… Show more

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Cited by 86 publications
(67 citation statements)
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“…Moreover, these γδ-T cells were producing IL-17 ( Fig. 2G), causing damage rather than tolerance as suggested previously (7,(17)(18)(19)(20).…”
Section: Resultsmentioning
confidence: 54%
“…Moreover, these γδ-T cells were producing IL-17 ( Fig. 2G), causing damage rather than tolerance as suggested previously (7,(17)(18)(19)(20).…”
Section: Resultsmentioning
confidence: 54%
“…Real-time quantitative PCR (RT-qPCR) analysis of myeloperoxidase (MPO), a marker for activated neutrophils (38), confirmed the defective neutrophilic inflammation in Lxra -/-Lxrb -/-and Lxra -/-mice 7 days after infection, showing only basal mRNA levels in the lung tissue ( Figure 5B). Furthermore, CD11c + lung cells from Lxra -/-Lxrb -/-mice expressed lower mRNA levels of the neutrophil-attracting chemokines keratinocyte-derived chemokine (KC) and LPS-induced chemokine (LIX) as well as of IL-23, a cytokine implicated in the regulation of granulopoiesis and the prevalence of IL-17-producing cells (39), compared with cells from WT mice ( Figure 5C). In agreement with our bacillary growth findings, CD11c + lung cells from Lxra -/-mice, but not Lxrb -/-mice, mimicked the blunted neutrophil-attracting chemokine and cytokine response observed in the Lxra -/-Lxrb -/-mice.…”
Section: Resultsmentioning
confidence: 99%
“…Lxra -/-mice also mimicked the abrogated airway neutrophilia observed in Lxra -/-Lxrb -/-mice early after infection. This was further reflected by the function of CD11c + lung cells, showing a defective capacity to express the neutrophil-attracting chemokines KC and LIX as well as IL-23p19, a known regulator of granulopoiesis and instructive cytokine for IL-17-producing T cells (39). The role of neutrophils early in mycobacterial infections remains a subject of controversy.…”
Section: Discussionmentioning
confidence: 99%
“…5, A and B). Because coronin 1 deletion results in a depletion of peripheral T cells (14) and neutrophil migration in vivo depends on cytokines produced by T cells (20,21) we analyzed the capacity of neutrophils to migrate in either WT or coronin 1-deficient mice. Before the analysis of in vivo chemotaxis, the number of circulating neutrophils were determined by analyzing the blood composition of WT and coronin 1-deficient mice using an ADVIA hematology system.…”
Section: Chemotaxis Of Neutrophils In the Presence And Absence Of Cormentioning
confidence: 99%