Homeostasis of IL-15 dependent lymphocyte subsets in the liver. (June 2016)

• Record Type: Journal Article
• Authors: Cepero-Donates, Yuneivy; Rakotoarivelo, Volatiana; Mayhue, Marian; Ma, Averil; Chen, Yi-Guang; Ramanathan, Sheela
• Is Part Of: Cytokine. Volume 82(2016)
• Page Start: 95
• Page End: 101
• Publication Date: 2016-06
• Subjects: NAFLD non-alcoholic fatty liver disease -- NASH non-alcoholic steatohepatitis -- IHL intrahepatic lymphocytes; Interleukin-15 -- Liver -- NAFLD; Cytokines -- Periodicals; 571.844
• DOI: 10.1016/j.cyto.2015.12.012
• Languages: English
• ISSNs: 1043-4666

Abstract

Highlights: Hepatocyte and macrophage-specific IL-15Rα maintains NK and NKT cells in the liver. NAFLD occurs even in the absence of NK and NKT cells in the liver. Absence of IL-15 or IL-15Rα does not influence the number of intrahepatic CD8 + T cells. Abstract: IL-15 is a member of the gamma chain family of cytokines (γc – CD132). The IL-15 receptor (IL-15R) complex consists of 3 subunits: the ligand-binding IL-15Rα chain (CD215), the β chain (CD122; also used by IL-2), and the common γ chain. The biological activities of IL-15 are mostly mediated by the IL-15:IL-15Rα complex, produced by the same cell and ' trans-presented ' to responder cells expressing the IL-15Rβγc . The peculiar and almost unique requirement for IL-15 to be trans-presented by IL-15Rα 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-15Rα has shown macrophage-and dendritic cell-derived IL-15Rα mediate the homeostasis of different CD8 + T cell subsets. Here we show that hepatocyte and macrophage- specific expression of IL-15Rα 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.