Adipocyte IL-15 regulates local and systemic NK cell development

J Immunol. 2014 Aug 15;193(4):1747-58. doi: 10.4049/jimmunol.1400868. Epub 2014 Jul 9.

Abstract

NK cell development and homeostasis require IL-15 produced by both hematopoietic and parenchymal cells. Certain hematopoietic IL-15 sources, such as macrophages and dendritic cells, are known, whereas the source of parenchymal IL-15 remains elusive. Using two types of adipocyte-specific Il15(-/-) mice, we identified adipocytes as a parenchymal IL-15 source that supported NK cell development nonredundantly. Both adipocyte-specific Il15(-/-) mice showed reduced IL-15 production specifically in the adipose tissue but impaired NK cell development in the spleen and liver in addition to the adipose tissue. We also found that the adipose tissue harbored NK progenitors as other niches (e.g. spleen) for NK cell development, and that NK cells derived from transplanted adipose tissue populated the recipient's spleen and liver. These findings suggest that adipocyte IL-15 contributes to systemic NK cell development by supporting NK cell development in the adipose tissue, which serves as a source of NK cells for other organs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipocytes / cytology*
  • Adipocytes / immunology
  • Adipocytes / transplantation
  • Adipose Tissue / immunology
  • Adoptive Transfer
  • Animals
  • Bone Marrow Cells / immunology
  • Cell Differentiation / immunology*
  • Dendritic Cells / immunology
  • Homeostasis / immunology
  • Interleukin-15 / genetics
  • Interleukin-15 / immunology*
  • Killer Cells, Natural / cytology*
  • Killer Cells, Natural / immunology
  • Killer Cells, Natural / transplantation
  • Lectins, C-Type
  • Liver / cytology
  • Macrophages / immunology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • NK Cell Lectin-Like Receptor Subfamily A / biosynthesis
  • RNA, Messenger / biosynthesis
  • Receptors, Immunologic / biosynthesis
  • Spleen / cytology

Substances

  • Interleukin-15
  • Klra3 protein, mouse
  • Klrg1 protein, mouse
  • Lectins, C-Type
  • NK Cell Lectin-Like Receptor Subfamily A
  • RNA, Messenger
  • Receptors, Immunologic