title: Neutrophils are essential as a source of IL-17 in the effector phase of arthritis.
abstract: OBJECTIVE
  Th17 has been shown to have a pivotal role in the development of arthritis. However, the role of IL-17 in the T cell-independent effector phase has not fully been examined. We investigated whether IL-17 is involved in the effector phase of arthritis by using K/BxN serum-induced arthritis model.
  
  
  METHODS
  K/BxN serum was transferred into IL-17 knockout (KO) mice, SCID mice and their control mice, and arthritis was evaluated over time. In order to clarify the source of IL-17 in the effector phase, neutrophils or CD4+ T cells collected from IL-17 KO or control mice were injected into IL-17 KO recipient mice together with K/BxN serum. To examine if neutrophils secrete IL-17 upon stimulation, neutrophils were stimulated with immune complex in vitro and IL-17 in the supernatant was measured by ELISA.
  
  
  RESULTS
  K/BxN serum-induced arthritis was much less severe in IL-17 KO mice than in WT mice. Since K/BxN serum-transferred SCID mice developed severe arthritis with high serum IL-17 concentration, we speculated neutrophils are the responsible player as an IL-17 source. When wild type (WT) but not IL-17 KO neutrophils were co-injected with K/BxN serum into IL-17 KO mice, arthritis was exacerbated, whereas co-injection of WT CD4+ T cells had no effect. In vitro, stimulation of neutrophils with immune complex caused IL-17 secretion.
  
  
  CONCLUSIONS
  Neutrophils are essential as a source of IL-17 in the effector phase of arthritis. The trigger of secreting IL-17 from neutrophils may be immune complex.
authors.affiliation: Department of Rheumatology and Clinical Immunology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Katayama
authors.forename: Koichiro
authors.initials: K
authors.lastname: Ohmura
authors.forename: Naoichiro
authors.initials: N
authors.lastname: Yukawa
authors.forename: Chikashi
authors.initials: C
authors.lastname: Terao
authors.forename: Motomu
authors.initials: M
authors.lastname: Hashimoto
authors.forename: Hajime
authors.initials: H
authors.lastname: Yoshifuji
authors.forename: Daisuke
authors.initials: D
authors.lastname: Kawabata
authors.forename: Takao
authors.initials: T
authors.lastname: Fujii
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Iwakura
authors.forename: Tsuneyo
authors.initials: T
authors.lastname: Mimori
mesh_terms: D000818:Animals; D000843:Ankle Joint / Q000378:metabolism / Q000473:pathology; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000276:immunology* / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000637:transplantation; D002478:Cells, Cultured; D020381:Interleukin-17 / Q000097:blood* / Q000235:genetics / Q000378:metabolism; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D016688:Mice, Inbred NOD; D018345:Mice, Knockout; D016513:Mice, SCID; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism*
chemical_list: D020381:Interleukin-17