title: Essential roles of DC-derived IL-15 as a mediator of inflammatory responses in vivo.
abstract: Interleukin (IL)-15 is expressed in a variety of inflammatory diseases. However, the contribution of dendritic cell (DC)-derived IL-15 to the development of diseases is uncertain. Using established models of Propionibacterium acnes (P. acnes)- and zymosan-induced liver inflammation, we observed granuloma formation in the livers of wild-type (WT) and RAG-2(-/-) mice but not in those of IL-15(-/-) mice. We demonstrate that this is likely caused by an impaired sequential induction of IL-12, IFN-gamma, and chemokines necessary for monocyte migration. Likewise, lethal endotoxin shock was not induced in P. acnes- and zymosan-primed IL-15(-/-) mice or in WT mice treated with a new IL-15-neutralizing antibody. In both systems, proinflammatory cytokine production was impaired. Surprisingly, neither granuloma formation, lethal endotoxin shock, nor IL-15 production was induced in mice deficient for DCs, and adoptive transfer of WT but not IL-15(-/-) DCs restored the disease development in IL-15(-/-) mice. Collectively, these data indicate the importance of DC-derived IL-15 as a mediator of inflammatory responses in vivo.
authors.affiliation: Department of Immunology, Akita University School of Medicine, Akita 010-8543, Japan. tohteki@med.akita-u.ac.jp
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Ohteki
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Tada
authors.forename: Kazuto
authors.initials: K
authors.lastname: Ishida
authors.forename: Taku
authors.initials: T
authors.lastname: Sato
authors.forename: Chikako
authors.initials: C
authors.lastname: Maki
authors.forename: Taketo
authors.initials: T
authors.lastname: Yamada
authors.forename: Junji
authors.initials: J
authors.lastname: Hamuro
authors.forename: Shigeo
authors.initials: S
authors.lastname: Koyasu
mesh_terms: D000818:Animals; D003713:Dendritic Cells / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D006099:Granuloma / Q000276:immunology*; D006505:Hepatitis / Q000276:immunology* / Q000382:microbiology; D007150:Immunohistochemistry; D019409:Interleukin-15 / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D011425:Propionibacterium acnes; D015054:Zymosan
chemical_list: D019409:Interleukin-15; D015054:Zymosan