Critical role of IL-15–IL-15R for antigen-presenting cell functions in the innate immune response


Activation of dendritic cells (DCs) and macrophages by infectious agents leads to secretion of interleukin 12 (IL-12), which subsequently induces interferon-γ (IFN-γ) production by multiple cell types that include DCs and macrophages. In turn, IFN-γ acts on macrophages to augment IL-12 secretion and to produce nitric oxide (NO), which eradicates infected microbes. We show here that in cytokine common γ subunit–deficient and/or IL-2 receptor β–deficient mice, production of IL-12, IFN-γ and NO by DCs and macrophages was severely impaired, as was up-regulation of major histocompatibility complex class II and CD40. Similar phenotypes were observed in DCs and macrophages from IL-15–deficient mice but not in those from IL-2–deficient mice. This shows that the IL-15–IL-15R interaction is critical in early activation of antigen-presenting cells and plays an important role in the innate immune system.

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Figure 1: Presence of macrophages and DCs in the spleens of γc−/−(Y)RAG-2−/−, IL-2Rβ−/−RAG-2−/− and NK-depleted RAG-2−/− mice.
Figure 2: Signals from γc and IL-2Rβ subunits regulate production of IL-12, IFN-γ and NO by APCs.
Figure 3: Impaired up-regulation of MHC class II and CD40 on IL-2Rβ−/− RAG-2−/− and IL-15−/− macrophages.
Figure 4: Essential roles of IL-15 in APC production of IL-12 and the responsiveness of APCs to IL-12.


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We thank K. Sugamura for the Tum122 and TUGm2 mAbs. Supported by the Ministry of Education, Culture, Sports, Science and Technology, Japan (grant 13214095 to T. O.); the Naito Foundation (to T. O.); the Japan Society for the Promotion of Science (13GS0015); a National Grant-in-Aid for the Establishment of a High-Tech Research Center in a private University; a Keio University Special Grant-in-Aid for Innovative Collaborative Research Project; a grant from the Japan Society for the Promotion of Science (JSPS-RFTF-97L00701); a Scientific Frontier Research Grant from the Ministry of Education, Culture, Sports, Science and Technology, Japan; and the Japan Society for the Promotion of Science for Young Scientists (to K. S.)

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Correspondence to Shigeo Koyasu.

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Ohteki, T., Suzue, K., Maki, C. et al. Critical role of IL-15–IL-15R for antigen-presenting cell functions in the innate immune response. Nat Immunol 2, 1138–1143 (2001) doi:10.1038/ni729

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