Steady-state production of IL-4 modulates immunity in mouse strains and is determined by lineage diversity of iNKT cells

Nat Immunol. 2013 Nov;14(11):1146-54. doi: 10.1038/ni.2731. Epub 2013 Oct 6.


Invariant natural killer T cells (iNKT cells) can produce copious amounts of interleukin 4 (IL-4) early during infection. However, indirect evidence suggests they may produce this immunomodulatory cytokine in the steady state. Through intracellular staining for transcription factors, we have defined three subsets of iNKT cells (NKT1, NKT2 and NKT17) that produced distinct cytokines; these represented diverse lineages and not developmental stages, as previously thought. These subsets exhibited substantial interstrain variation in numbers. In several mouse strains, including BALB/c, NKT2 cells were abundant and were stimulated by self ligands to produce IL-4. In those strains, steady-state IL-4 conditioned CD8(+) T cells to become 'memory-like', increased serum concentrations of immunoglobulin E (IgE) and caused dendritic cells to produce chemokines. Thus, iNKT cell-derived IL-4 altered immunological properties under normal steady-state conditions.

Publication types

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

MeSH terms

  • Age Factors
  • Animals
  • Antigens, CD / genetics
  • Antigens, CD / immunology
  • CD8-Positive T-Lymphocytes / cytology
  • CD8-Positive T-Lymphocytes / immunology
  • Cell Lineage / immunology*
  • Dendritic Cells / cytology
  • Dendritic Cells / immunology
  • GATA3 Transcription Factor / genetics
  • GATA3 Transcription Factor / immunology
  • Gene Expression Regulation
  • Genetic Variation / immunology
  • Immunity, Innate*
  • Immunoglobulin E / genetics
  • Immunoglobulin E / immunology
  • Immunologic Memory
  • Immunophenotyping
  • Interleukin-4 / biosynthesis*
  • Interleukin-4 / immunology
  • Kruppel-Like Transcription Factors / genetics
  • Kruppel-Like Transcription Factors / immunology
  • Mice
  • Natural Killer T-Cells / cytology
  • Natural Killer T-Cells / immunology*
  • Promyelocytic Leukemia Zinc Finger Protein
  • Species Specificity
  • T-Box Domain Proteins / genetics
  • T-Box Domain Proteins / immunology


  • Antigens, CD
  • GATA3 Transcription Factor
  • Gata3 protein, mouse
  • Kruppel-Like Transcription Factors
  • Promyelocytic Leukemia Zinc Finger Protein
  • T-Box Domain Proteins
  • T-box transcription factor TBX21
  • Zbtb16 protein, mouse
  • Interleukin-4
  • Immunoglobulin E