共 49 条
IL-23 is required for neutrophil homeostasis in normal and neutrophilic mice
被引:78
作者:

Smith, Emily
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机构:
Univ Virginia, Robert M Berne Cardiovasc Res Ctr, Charlottesville, VA 22908 USA Univ Virginia, Robert M Berne Cardiovasc Res Ctr, Charlottesville, VA 22908 USA

Zarbock, Alexander
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机构:
Univ Virginia, Robert M Berne Cardiovasc Res Ctr, Charlottesville, VA 22908 USA
Univ Munster, Dept Anesthesiol & Crit Care Med, Munster, Germany
La Jolla Inst Allergy & Immunol, Div Inflammat Biol, La Jolla, CA 92037 USA Univ Virginia, Robert M Berne Cardiovasc Res Ctr, Charlottesville, VA 22908 USA

Stark, Matthew A.
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机构:
Univ Virginia, Dept Biomed Engn, Charlottesville, VA 22908 USA
Univ Virginia, Dept Mol Physiol & Biol Phys, Charlottesville, VA 22908 USA Univ Virginia, Robert M Berne Cardiovasc Res Ctr, Charlottesville, VA 22908 USA

Burcin, Tracy L.
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机构:
Univ Virginia, Dept Biomed Engn, Charlottesville, VA 22908 USA
Univ Virginia, Dept Mol Physiol & Biol Phys, Charlottesville, VA 22908 USA Univ Virginia, Robert M Berne Cardiovasc Res Ctr, Charlottesville, VA 22908 USA

Bruce, Anthony C.
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机构:
Univ Virginia, Dept Biomed Engn, Charlottesville, VA 22908 USA
Univ Virginia, Dept Mol Physiol & Biol Phys, Charlottesville, VA 22908 USA Univ Virginia, Robert M Berne Cardiovasc Res Ctr, Charlottesville, VA 22908 USA

Foley, Patricia
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机构:
Univ Virginia, Off Vice President Res & Grad Studies, Charlottesville, VA 22908 USA Univ Virginia, Robert M Berne Cardiovasc Res Ctr, Charlottesville, VA 22908 USA

Ley, Klaus
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h-index: 0
机构: Univ Virginia, Robert M Berne Cardiovasc Res Ctr, Charlottesville, VA 22908 USA
机构:
[1] Univ Virginia, Robert M Berne Cardiovasc Res Ctr, Charlottesville, VA 22908 USA
[2] Univ Virginia, Dept Biomed Engn, Charlottesville, VA 22908 USA
[3] Univ Virginia, Dept Mol Physiol & Biol Phys, Charlottesville, VA 22908 USA
[4] Univ Virginia, Off Vice President Res & Grad Studies, Charlottesville, VA 22908 USA
[5] Univ Munster, Dept Anesthesiol & Crit Care Med, Munster, Germany
[6] La Jolla Inst Allergy & Immunol, Div Inflammat Biol, La Jolla, CA 92037 USA
关键词:
D O I:
10.4049/jimmunol.179.12.8274
中图分类号:
R392 [医学免疫学];
Q939.91 [免疫学];
学科分类号:
100102 ;
摘要:
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 gamma delta TCR. This homeostatic system is disrupted in mice lacking adhesion molecules like beta(2)-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 beta(2)-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 gamma delta(+) 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.
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页码:8274 / 8279
页数:6
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