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.
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.
authors.affiliation: Department of Ophthalmology and Visual Sciences, Case Western Reserve University, Cleveland, Ohio, USA.
authors.forename: Patricia R
authors.initials: PR
authors.lastname: Taylor
authors.affiliation: 1] Department of Ophthalmology and Visual Sciences, Case Western Reserve University, Cleveland, Ohio, USA. [2].
authors.forename: Sanhita
authors.initials: S
authors.lastname: Roy
authors.affiliation: 1] Department of Ophthalmology and Visual Sciences, Case Western Reserve University, Cleveland, Ohio, USA. [2].
authors.forename: Sixto M
authors.initials: SM
authors.lastname: Leal
authors.affiliation: Department of Ophthalmology and Visual Sciences, Case Western Reserve University, Cleveland, Ohio, USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Ophthalmology and Visual Sciences, Case Western Reserve University, Cleveland, Ohio, USA.
authors.forename: Scott J
authors.initials: SJ
authors.lastname: Howell
authors.affiliation: Department of Pathology, Case Western Reserve University, Cleveland, Ohio, USA.
authors.forename: Brian A
authors.initials: BA
authors.lastname: Cobb
authors.affiliation: Department of Immunology, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio, USA.
authors.forename: Xiaoxia
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Ophthalmology and Visual Sciences, Case Western Reserve University, Cleveland, Ohio, USA.
authors.forename: Eric
authors.initials: E
authors.lastname: Pearlman
mesh_terms: D000818:Animals; D001228:Aspergillosis / Q000150:complications / Q000276:immunology*; D001230:Aspergillus / Q000276:immunology*; D019898:Autocrine Communication; D001854:Bone Marrow Cells / Q000276:immunology; D015550:Cell Degranulation; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic / Q000235:genetics; D004195:Disease Models, Animal; D006801:Humans; D020381:Interleukin-17 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D053759:Interleukin-23 / Q000276:immunology; D015850:Interleukin-6 / Q000276:immunology; D007634:Keratitis / Q000209:etiology / Q000276:immunology*; D037181:Lectins, C-Type / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009504:Neutrophils / Q000276:immunology*; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D018123:Receptors, Interleukin / Q000378:metabolism*
chemical_list: C448419:IL17RC protein, human; C508527:Il17rc protein, mouse; D020381:Interleukin-17; D053759:Interleukin-23; D015850:Interleukin-6; D037181:Lectins, C-Type; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D017382:Reactive Oxygen Species; D018123:Receptors, Interleukin; C445340:dectin-2, mouse