title: In vivo induction of cutaneous inflammation results in the accumulation of extracellular trap-forming neutrophils expressing RORγt and IL-17.
abstract: Clinical trials successfully using antibodies targeting IL-17 in psoriasis support the importance of IL-17 in the pathophysiology of this disease. However, there is a debate concerning the source and dynamics of IL-17 production in inflamed skin. Here we characterized IL-17-producing immune cells over time, using two established in vivo models of human skin inflammation that share many histological features with psoriasis, i.e., leukotriene B4 application and tape-stripping. Both treatments revealed a clear influx of neutrophils and T cells. Staining for IL-17 revealed that the majority of IL-17 was expressed by neutrophils and mast cells, in both models. Neutrophils, but not mast cells, coexpressed the IL-17-associated transcription factor RORγt and were able to form extracellular traps. While the presence of mast cells remained steady during the skin inflammatory process, the presence of neutrophils was clearly dynamic in time. Therefore, it is attractive to hypothesize that IL-17+/RORγt+ neutrophils contribute to human skin inflammation in vivo and possibly to the pathogenesis of skin diseases such as psoriasis. Surprisingly, T cells represented a minority of the IL-17-expressing cell population. These observations challenge the classical opinion that IL-17 is predominantly associated with T cells in skin inflammation.
authors: Department of Dermatology, Radboud University Medical Center, Nijmegen, The Netherlands; Department of Laboratory Medicine, Laboratory of Medical Immunology, Radboud University Medical Center, Nijmegen, The Netherlands; Nijmegen Institute for Infection, Inflammation and Immunity (N4i), Nijmegen, The Netherlands. Electronic address: Romy.Keijsers@radboudumc.nl.
authors: Romy R M C
authors: RRMC
authors: Keijsers
authors: Department of Dermatology, Radboud University Medical Center, Nijmegen, The Netherlands; Nijmegen Institute for Infection, Inflammation and Immunity (N4i), Nijmegen, The Netherlands.
authors: Anke G M
authors: AGM
authors: Hendriks
authors: Department of Dermatology, Radboud University Medical Center, Nijmegen, The Netherlands; Nijmegen Institute for Infection, Inflammation and Immunity (N4i), Nijmegen, The Netherlands.
authors: Piet E J
authors: PEJ
authors: van Erp
authors: Department of Laboratory Medicine, Laboratory of Medical Immunology, Radboud University Medical Center, Nijmegen, The Netherlands.
authors: Bram
authors: B
authors: van Cranenbroek
authors: Department of Dermatology, Radboud University Medical Center, Nijmegen, The Netherlands; Nijmegen Institute for Infection, Inflammation and Immunity (N4i), Nijmegen, The Netherlands.
authors: Peter C M
authors: PCM
authors: van de Kerkhof
authors: Department of Laboratory Medicine, Laboratory of Medical Immunology, Radboud University Medical Center, Nijmegen, The Netherlands; Nijmegen Institute for Infection, Inflammation and Immunity (N4i), Nijmegen, The Netherlands.
authors: Hans J P M
authors: HJPM
authors: Koenen
authors: Department of Laboratory Medicine, Laboratory of Medical Immunology, Radboud University Medical Center, Nijmegen, The Netherlands; Nijmegen Institute for Infection, Inflammation and Immunity (N4i), Nijmegen, The Netherlands.
authors: Irma
authors: I
authors: Joosten
mesh_terms: D056704:Adaptive Immunity / Q000276:immunology; D000293:Adolescent; D000328:Adult; D001706:Biopsy; D003872:Dermatitis / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology; D020381:Interleukin-17 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D007975:Leukotriene B4 / Q000008:administration & dosage; D008297:Male; D008407:Mast Cells / Q000276:immunology / Q000378:metabolism; D008875:Middle Aged; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology*; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D011565:Psoriasis / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D012867:Skin / Q000187:drug effects / Q000276:immunology; D053832:Surgical Tape / Q000009:adverse effects; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism; D055815:Young Adult
chemical_list: C508717:IL17A protein, human; D020381:Interleukin-17; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; C539900:RORC protein, human; D007975:Leukotriene B4