Essential roles of DC-derived IL-15 as a mediator of inflammatory responses in vivo

Toshiaki Ohteki, Hiroyuki Tada, Kazuto Ishida, Taku Sato, Chikako Maki, Taketo Yamada, Junji Hamuro, Shigeo Koyasu

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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-γ, 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. JEM

Original languageEnglish
Pages (from-to)2329-2338
Number of pages10
JournalJournal of Experimental Medicine
Volume203
Issue number10
DOIs
Publication statusPublished - 2006

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Interleukin-15
Dendritic Cells
Propionibacterium acnes
Zymosan
Granuloma
Endotoxins
Shock
Adoptive Transfer
Liver
Interleukin-12
Neutralizing Antibodies
Chemokines
Monocytes
Cytokines
Inflammation

ASJC Scopus subject areas

  • Immunology

Cite this

Ohteki, T., Tada, H., Ishida, K., Sato, T., Maki, C., Yamada, T., ... Koyasu, S. (2006). Essential roles of DC-derived IL-15 as a mediator of inflammatory responses in vivo. Journal of Experimental Medicine, 203(10), 2329-2338. https://doi.org/10.1084/jem.20061297

Essential roles of DC-derived IL-15 as a mediator of inflammatory responses in vivo. / Ohteki, Toshiaki; Tada, Hiroyuki; Ishida, Kazuto; Sato, Taku; Maki, Chikako; Yamada, Taketo; Hamuro, Junji; Koyasu, Shigeo.

In: Journal of Experimental Medicine, Vol. 203, No. 10, 2006, p. 2329-2338.

Research output: Contribution to journalArticle

Ohteki, T, Tada, H, Ishida, K, Sato, T, Maki, C, Yamada, T, Hamuro, J & Koyasu, S 2006, 'Essential roles of DC-derived IL-15 as a mediator of inflammatory responses in vivo', Journal of Experimental Medicine, vol. 203, no. 10, pp. 2329-2338. https://doi.org/10.1084/jem.20061297
Ohteki, Toshiaki ; Tada, Hiroyuki ; Ishida, Kazuto ; Sato, Taku ; Maki, Chikako ; Yamada, Taketo ; Hamuro, Junji ; Koyasu, Shigeo. / Essential roles of DC-derived IL-15 as a mediator of inflammatory responses in vivo. In: Journal of Experimental Medicine. 2006 ; Vol. 203, No. 10. pp. 2329-2338.
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