| First Author | Chenoweth MJ | Year | 2012 |
| Journal | J Immunol | Volume | 188 |
| Issue | 9 | Pages | 4149-57 |
| PubMed ID | 22447977 | Mgi Jnum | J:188467 |
| Mgi Id | MGI:5440579 | Doi | 10.4049/jimmunol.1101883 |
| Citation | Chenoweth MJ, et al. (2012) IL-15 can signal via IL-15Ralpha, JNK, and NF-kappaB to drive RANTES production by myeloid cells. J Immunol 188(9):4149-57 |
| abstractText | IL-15 plays many important roles within the immune system. IL-15 signals in lymphocytes via trans presentation, where accessory cells such as macrophages and dendritic cells present IL-15 bound to IL-15Ralpha in trans to NK cells and CD8(+) memory T cells expressing IL-15/IL-2Rbeta and common gamma chain (gamma(c)). Previously, we showed that the prophylactic delivery of IL-15 to Rag2(-/-)gamma(c)(-/-) mice (mature T, B, and NK cell negative) afforded protection against a lethal HSV-2 challenge and metastasis of B16/F10 melanoma cells. In this study, we demonstrated that in vivo delivery of an adenoviral construct optimized for the secretion of human IL-15 to Rag2(-/-)gamma(c)(-/-) mice resulted in significant increases in spleen size and cell number, leading us to hypothesize that IL-15 signals differently in myeloid immune cells compared with lymphocytes, for which IL-15/IL-2Rbeta and gamma(c) expression are essential. Furthermore, treatment with IL-15 induced RANTES production by Rag2(-/-)gamma(c)(-/-) bone marrow cells, but the presence of gamma(c) did not increase bone marrow cell sensitivity to IL-15. This IL-15-mediated RANTES production by Rag2(-/-)gamma(c)(-/-) bone marrow cells occurred independently of the IL-15/IL-2Rbeta and Jak/STAT pathways and instead required IL-15Ralpha signaling as well as activation of JNK and NF-kappaB. Importantly, we also showed that the trans presentation of IL-15 by IL-15Ralpha boosts IL-15-mediated IFN-gamma production by NK cells but reduces IL-15-mediated RANTES production by Rag2(-/-)gamma(c)(-/-) myeloid bone marrow cells. Our data clearly show that IL-15 signaling in NK cells is different from that of myeloid immune cells. Additional insights into IL-15 biology may lead to novel therapies aimed at bolstering targeted immune responses against cancer and infectious disease. |
