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 RAG2(-/-) 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 zymosanprimed IL- 15(-/-) mice or in WT mice treated with a new IL-15 - neutralizing antibody. In both systems, proinfl ammatory cytokine production was impaired. Surprisingly, neither granuloma formation, lethal endotoxin shock, nor IL-15 production was induced in mice defi cient 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 infl ammatory responses in vivo.