Essential roles of DC-derived IL-15 as a mediator of inflammatory responses in vivo.
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.
Ohteki
Toshiaki
T
Department of Immunology, Akita University School of Medicine, Akita 010-8543, Japan. tohteki@med.akita-u.ac.jp
Tada
Hiroyuki
H
Ishida
Kazuto
K
Sato
Taku
T
Maki
Chikako
C
Yamada
Taketo
T
Hamuro
Junji
J
Koyasu
Shigeo
S
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
D019409:Interleukin-15; D015054:Zymosan