Tissue-resident natural killer (NK) cells are cell lineages distinct from thymic and conventional splenic NK cells

Elife. 2014 Jan 1;3:e01659. doi: 10.7554/eLife.01659.

Abstract

Natural killer (NK) cells belong to the innate immune system; they can control virus infections and developing tumors by cytotoxicity and producing inflammatory cytokines. Most studies of mouse NK cells, however, have focused on conventional NK (cNK) cells in the spleen. Recently, we described two populations of liver NK cells, tissue-resident NK (trNK) cells and those resembling splenic cNK cells. However, their lineage relationship was unclear; trNK cells could be developing cNK cells, related to thymic NK cells, or a lineage distinct from both cNK and thymic NK cells. Herein we used detailed transcriptomic, flow cytometric, and functional analysis and transcription factor-deficient mice to determine that liver trNK cells form a distinct lineage from cNK and thymic NK cells. Taken together with analysis of trNK cells in other tissues, there are at least four distinct lineages of NK cells: cNK, thymic, liver (and skin) trNK, and uterine trNK cells. DOI: http://dx.doi.org/10.7554/eLife.01659.001.

Keywords: liver; skin; uterus.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers / metabolism
  • Cell Lineage*
  • Cells, Cultured
  • Female
  • Flow Cytometry
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Immunophenotyping
  • Killer Cells, Natural / immunology*
  • Killer Cells, Natural / metabolism
  • Liver / cytology
  • Liver / immunology*
  • Liver / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Phenotype
  • Skin / cytology
  • Skin / immunology*
  • Skin / metabolism
  • Spleen / cytology
  • Spleen / immunology*
  • Spleen / metabolism
  • Thymus Gland / cytology
  • Thymus Gland / immunology*
  • Thymus Gland / metabolism
  • Transcription Factors / deficiency
  • Transcription Factors / genetics
  • Uterus / cytology
  • Uterus / immunology*
  • Uterus / metabolism

Substances

  • Biomarkers
  • Transcription Factors