Homeostasis of IL-15 dependent lymphocyte subsets in the liver

IL-15 is a member of the gamma chain family of cytokines (gamma(c) - CD132). The IL-15 receptor (IL-15R) complex consists of 3 subunits: the ligand-binding IL-15R alpha chain (CD215), the beta chain (CD122; also used by IL-2), and the common gamma chain. The biological activities of IL-15 are mostly mediated by the IL-15:IL-15R alpha complex, produced by the same cell and 'trans-presented' to responder cells expressing the IL-15R beta gamma(c). The peculiar and almost unique requirement for IL-15 to be trans-presented by IL-15R alpha suggests that the biological effects of IL-15 signaling are tightly regulated even at the level of availability of IL-15. Tissue-specific deletion of IL-15R alpha has shown macrophage-and dendritic cell-derived IL-15R alpha mediate the homeostasis of different CD8(+) T cell subsets. Here we show that hepatocyte and macrophage- specific expression of IL-15R alpha is required to maintain the homeostasis of NK and NKT cells in the liver. Thus, homeostasis of IL-15-dependent lymphocyte subsets is also regulated by trans-presentation of IL-15 by non-hematopoietic cells in the tissue environment. (C) 2015 Elsevier Ltd. All rights reserved.