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

Nat Immunol. 2014 Feb;15(2):143-51. doi: 10.1038/ni.2797. Epub 2013 Dec 22.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aspergillosis / complications
  • Aspergillosis / immunology*
  • Aspergillus / immunology*
  • Autocrine Communication
  • Bone Marrow Cells / immunology
  • Cell Degranulation
  • Cells, Cultured
  • Cytotoxicity, Immunologic / genetics
  • Disease Models, Animal
  • Humans
  • Interleukin-17 / genetics
  • Interleukin-17 / immunology
  • Interleukin-17 / metabolism*
  • Interleukin-23 / immunology
  • Interleukin-6 / immunology
  • Keratitis / etiology
  • Keratitis / immunology*
  • Lectins, C-Type / genetics
  • Lectins, C-Type / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Neutrophils / immunology*
  • Nuclear Receptor Subfamily 1, Group F, Member 3 / genetics
  • Nuclear Receptor Subfamily 1, Group F, Member 3 / metabolism
  • Reactive Oxygen Species / metabolism
  • Receptors, Interleukin / metabolism*


  • IL17RC protein, human
  • Il17rc protein, mouse
  • Interleukin-17
  • Interleukin-23
  • Interleukin-6
  • Lectins, C-Type
  • Nuclear Receptor Subfamily 1, Group F, Member 3
  • Reactive Oxygen Species
  • Receptors, Interleukin
  • dectin-2, mouse