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

Patricia R Taylor; Sanhita Roy; Sixto M Leal Jr; Yan Sun; Scott J Howell; Brian A Cobb; Xiaoxia Li; Eric Pearlman

doi:10.1038/ni.2797

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.

Authors

Patricia R Taylor¹, Sanhita Roy², Sixto M Leal Jr², Yan Sun¹, Scott J Howell¹, Brian A Cobb³, Xiaoxia Li⁴, Eric Pearlman¹

Affiliations

¹ Department of Ophthalmology and Visual Sciences, Case Western Reserve University, Cleveland, Ohio, USA.
² 1] Department of Ophthalmology and Visual Sciences, Case Western Reserve University, Cleveland, Ohio, USA. [2].
³ Department of Pathology, Case Western Reserve University, Cleveland, Ohio, USA.
⁴ Department of Immunology, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio, USA.

PMID: 24362892
PMCID: PMC3972892
DOI: 10.1038/ni.2797

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.

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*

Substances

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

Abstract

Publication types

MeSH terms

Substances

Grants and funding