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

Research output: Contribution to journalArticlepeer-review

63 Citations (Scopus)

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

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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