The heterogeneity of human CD127(+) innate lymphoid cells revealed by single-cell RNA sequencing

Nat Immunol. 2016 Apr;17(4):451-60. doi: 10.1038/ni.3368. Epub 2016 Feb 15.


Innate lymphoid cells (ILCs) are increasingly appreciated as important participants in homeostasis and inflammation. Substantial plasticity and heterogeneity among ILC populations have been reported. Here we have delineated the heterogeneity of human ILCs through single-cell RNA sequencing of several hundreds of individual tonsil CD127(+) ILCs and natural killer (NK) cells. Unbiased transcriptional clustering revealed four distinct populations, corresponding to ILC1 cells, ILC2 cells, ILC3 cells and NK cells, with their respective transcriptomes recapitulating known as well as unknown transcriptional profiles. The single-cell resolution additionally divulged three transcriptionally and functionally diverse subpopulations of ILC3 cells. Our systematic comparison of single-cell transcriptional variation within and between ILC populations provides new insight into ILC biology during homeostasis, with additional implications for dysregulation of the immune system.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Child
  • Child, Preschool
  • Female
  • Flow Cytometry
  • Gene Expression Profiling
  • Humans
  • Immunity, Innate / immunology
  • Interleukin-7 Receptor alpha Subunit / metabolism*
  • Killer Cells, Natural / immunology
  • Killer Cells, Natural / metabolism*
  • Leukocytes, Mononuclear / immunology
  • Leukocytes, Mononuclear / metabolism*
  • Lymphocyte Subsets / immunology
  • Lymphocyte Subsets / metabolism*
  • Lymphocytes / immunology
  • Lymphocytes / metabolism*
  • Male
  • Middle Aged
  • Palatine Tonsil / cytology
  • Palatine Tonsil / immunology
  • Polymerase Chain Reaction
  • Sequence Analysis, RNA
  • Young Adult


  • Interleukin-7 Receptor alpha Subunit