title: Critical role of Th17 cells in inflammation and neovascularization after ischaemia.
abstract: OBJECTIVE
  Increasing evidence suggests that CD4(+) T cells contribute to neovascularization in ischaemic tissue. However, the T cell subset responsible for neovascularization after ischaemia remains to be determined. Here, we investigated the role of Th17 cells secreting interleukin (IL)-17, a newly identified subset of CD4(+) T cells, in the neovascularization after murine hindlimb ischaemia.
  
  
  RESULTS
  Unilateral hindlimb ischaemia was produced in wild-type (WT) C57BL/6 mice. Depletion of CD4(+) T cells resulted in significantly reduced blood flow perfusion in the ischaemic limbs. The expression of IL-17 and retinoic acid receptor-related orphan receptor γt (RORγt) was up-regulated in the ischaemic limbs. IL-17-deficient mice showed a significant reduction in blood flow perfusion, inflammatory cell infiltration, and production of angiogenic cytokines in the ischaemic limbs compared with WT mice. In bone marrow transplantation experiments, the absence of IL-17 specifically in bone marrow cells diminished the neovascularization after ischaemia. Furthermore, IL-17-deficient CD4(+) T cells transferred into the ischaemic limbs of T cell-deficient athymic nude mice evoked a significantly limited neovascularization compared with WT CD4(+) T cells.
  
  
  CONCLUSIONS
  These findings identify Th17 cells as a new angiogenic T cell subset and provide new insight into the mechanism by which T cells promote neovascularization after ischaemia.
authors.affiliation: Department of Cardiovascular Medicine, Shinshu University Graduate School of Medicine, Matsumoto, Japan.
authors.forename: Takeki
authors.initials: T
authors.lastname: Hata
authors.forename: Masafumi
authors.initials: M
authors.lastname: Takahashi
authors.forename: Shigeaki
authors.initials: S
authors.lastname: Hida
authors.forename: Masanori
authors.initials: M
authors.lastname: Kawaguchi
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Kashima
authors.forename: Fumitake
authors.initials: F
authors.lastname: Usui
authors.forename: Hajime
authors.initials: H
authors.lastname: Morimoto
authors.forename: Akiyo
authors.initials: A
authors.lastname: Nishiyama
authors.forename: Atsushi
authors.initials: A
authors.lastname: Izawa
authors.forename: Jun
authors.initials: J
authors.lastname: Koyama
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Iwakura
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Taki
authors.forename: Uichi
authors.initials: U
authors.lastname: Ikeda
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology; D004195:Disease Models, Animal; D006614:Hindlimb / Q000098:blood supply; D036341:Intercellular Signaling Peptides and Proteins / Q000276:immunology; D007511:Ischemia / Q000276:immunology* / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D009000:Monocytes / Q000276:immunology; D018919:Neovascularization, Physiologic / Q000276:immunology*; D009504:Neutrophils / Q000276:immunology; D058504:Th17 Cells / Q000166:cytology / Q000276:immunology*; D014657:Vasculitis / Q000276:immunology* / Q000473:pathology
chemical_list: D016207:Cytokines; D036341:Intercellular Signaling Peptides and Proteins