@article{5e163691cbe64c62a9400135027d1de9,
title = "Phagocytosis of apoptotic neutrophils regulates granulopoiesis via IL-23 and IL-17",
abstract = "Homeostatic regulation of neutrophil production is thought to match neutrophil elimination to maintain approximately constant numbers in the blood. Here, we show that IL-17, a cytokine that regulates granulopoiesis through G-CSF, is made by γδ T cells and unconventional αβ T cells. These neutrophil-regulatory T cells (Tn) are expanded in mice that lack leukocyte adhesion molecules, which have neutrophilia and defective neutrophil trafficking. Normal neutrophils migrate to tissues, where they become apoptotic and are phagocytosed by macrophages and dendritic cells. This curbs phagocyte secretion of IL-23, a cytokine controlling IL-17 production by Tn cells. Adoptive transfer of wild-type, but not adhesion molecule-deficient, neutrophils into mice deficient in β2 integrins transiently decreases neutrophilia and reduces levels of serum IL-17. Antibody blockade of the p40 subunit of IL-23 reduces neutrophil numbers in wild-type mice. These findings identify a major homeostatic mechanism for the regulation of neutrophil production in vivo.",
author = "Stark, {Matthew A.} and Yuqing Huo and Burcin, {Tracy L.} and Morris, {Margaret A.} and Olson, {Timothy S.} and Klaus Ley",
note = "Funding Information: We thank Dr. Kodi Ravichandaran, University of Virginia, for valuable discussion. We are grateful for Dr. Austin L. Gurney{\textquoteright}s (Genentech, San Francisco, CA) gift of recombinant IL-23. We also thank Dr. Arthur L. Beaudet (Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX), Dr. Christie M. Ballantyne (Department of Medicine, Baylor College of Medicine, Houston, TX), Dr. Daniel C. Bullard (Department of Comparative Medicine, University of Alabama-Birmingham, Birmingham, AL), Dr. Jamey D. Marth (Howard Hughes Medical Institute, Division of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA), Dr. Robert G. Collins (Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX), and Dr. Jacques J. Peschon (Amgen, Inc., Seattle, Washington) for providing breeding pairs of CD18 −/− , LFA-1 −/− , E/P −/− , Core2 −/− , E/P/L −/− , and IL-17R −/− mice, respectively. We also thank Drs. Theresa Pizarro and Jesus Rivera-Nieves (University of Virginia) for their kind gift of anti-p70 and anti-p40 antibodies. Finally, we appreciate Michele Kirkpatrick for her organization and animal husbandry. This work was supported by grants from the National Institutes of Health HL-54136 (K.L.) and T32 GM 08715-01A1 (M.A.S.) to Gordon Laurie and K.L. ",
year = "2005",
month = mar,
doi = "10.1016/j.immuni.2005.01.011",
language = "English (US)",
volume = "22",
pages = "285--294",
journal = "Immunity",
issn = "1074-7613",
publisher = "Cell Press",
number = "3",
}
