Activation of neutrophils by autocrine IL-17A-IL-17RC interactions during fungal infection is regulated by IL-6, IL-23, ROR gamma t and dectin-2

作者：Taylor, Patricia R.; Roy, Sanhita; Leal, Sixto M., Jr.; Sun, Yan; Howell, Scott J.; Cobb, Brian A.; Li, Xiaoxia; Pearlman, Eric^*

来源：Nature Immunology, 2014, 15(2): 143-151.

DOI：10.1038/ni.2797

• CHRONIC MUCOCUTANEOUS CANDIDIASIS
• PATTERN-RECOGNITION RECEPTOR
• BETA-GLUCAN RECEPTOR
• HOST-DEFENSE
• PROINFLAMMATORY IL-17(+)
• CELL-DIFFERENTIATION
• LECTIN RECEPTORS
• TH17 CELLS
• CYTOKINES
• ASPERGILLUS

Here we identified a population of bone marrow neutrophils that constitutively expressed the transcription factor ROR gamma t and produced and responded to interleukin 17A (IL-17A (IL-17)). IL-6, IL-23 and ROR gamma t, 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 ROR gamma t 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.

• 出版日期2014-2