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- Title
Activation of neutrophils by autocrine IL-17A-IL-17RC interactions during fungal infection is regulated by IL-6, IL-23, RORγt and dectin-2.
- Authors
Taylor, Patricia R; Roy, Sanhita; Leal, Sixto M; Sun, Yan; Howell, Scott J; Cobb, Brian A; Li, Xiaoxia; Pearlman, Eric
- Abstract
Here we identified a population of bone marrow neutrophils that constitutively expressed the transcription factor RORγt and produced and responded to interleukin 17A (IL-17A (IL-17)). IL-6, IL-23 and RORγt, but not T cells or natural killer (NK) cells, were required for IL-17 production in neutrophils. IL-6 and IL-23 induced expression of the receptors IL-17RC and dectin-2 on neutrophils, and IL-17RC expression was augmented by activation of dectin-2. Autocrine activity of IL-17A and its receptor induced the production of reactive oxygen species (ROS), and increased fungal killing in vitro and in a model of Aspergillus-induced keratitis. Human neutrophils also expressed RORγt and induced the expression of IL-17A, IL-17RC and dectin-2 following stimulation with IL-6 and IL-23. Our findings identify a population of human and mouse neutrophils with autocrine IL-17 activity that probably contribute to the etiology of microbial and inflammatory diseases.
- Subjects
NEUTROPHILS; AUTOCRINE mechanisms; INTERLEUKIN-17; MYCOSES; INTERLEUKIN-6; BONE marrow physiology; TRANSCRIPTION factors
- Publication
Nature Immunology, 2014, Vol 15, Issue 2, p143
- ISSN
1529-2908
- Publication type
Article
- DOI
10.1038/ni.2797