title: ifn-γ-dependent secretion of IL-10 from Th1 cells and microglia/macrophages contributes to functional recovery after spinal cord injury.
abstract: Transfer of type-1 helper T-conditioned (Th1-conditioned) cells promotes functional recovery with enhanced axonal remodeling after spinal cord injury (SCI). This study explored the molecular mechanisms underlying the beneficial effects of pro-inflammatory Th1-conditioned cells after SCI. The effect of Th1-conditioned cells from interferon-γ (ifn-γ) knockout mice (ifn-γ(-/-) Th1 cells) on the recovery after SCI was reduced. Transfer of Th1-conditioned cells led to the activation of microglia (MG) and macrophages (MΦs), with interleukin 10 (IL-10) upregulation. This upregulation of IL-10 was reduced when ifn-γ(-/-) Th1 cells were transferred. Intrathecal neutralization of IL-10 in the spinal cord attenuated the effects of Th1-conditioned cells. Further, IL-10 is robustly secreted from Th1-conditioned cells in an ifn-γ-dependent manner. Th1-conditioned cells from interleukin 10 knockout (il-10(-/-)) mice had no effects on recovery from SCI. These findings demonstrate that ifn-γ-dependent secretion of IL-10 from Th1 cells, as well as native MG/MΦs, is required for the promotion of motor recovery after SCI.
authors.affiliation: Department of Molecular Neuroscience, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Ishii
authors.forename: S
authors.initials: S
authors.lastname: Tanabe
authors.forename: M
authors.initials: M
authors.lastname: Ueno
authors.forename: T
authors.initials: T
authors.lastname: Kubo
authors.forename: H
authors.initials: H
authors.lastname: Kayama
authors.forename: S
authors.initials: S
authors.lastname: Serada
authors.forename: M
authors.initials: M
authors.lastname: Fujimoto
authors.forename: K
authors.initials: K
authors.lastname: Takeda
authors.forename: T
authors.initials: T
authors.lastname: Naka
authors.forename: T
authors.initials: T
authors.lastname: Yamashita
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D002478:Cells, Cultured; D005260:Female; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000378:metabolism; D016219:Immunotherapy, Adoptive; D007371:Interferon-gamma / Q000502:physiology*; D016753:Interleukin-10 / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017628:Microglia / Q000378:metabolism*; D009414:Nerve Growth Factors / Q000378:metabolism; D020127:Recovery of Function; D013119:Spinal Cord Injuries / Q000276:immunology / Q000628:therapy*; D018417:Th1 Cells / Q000378:metabolism* / Q000637:transplantation; D015854:Up-Regulation
chemical_list: D051100:Glial Cell Line-Derived Neurotrophic Factor; C556062:IL10 protein, mouse; D009414:Nerve Growth Factors; C518911:neurotropin 3, mouse; D016753:Interleukin-10; D007371:Interferon-gamma