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

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

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The Department of Laboratory Medicine and Pathology, Center for Immunology, University of Minnesota, Minneapolis, Minnesota, USA.

Erratum in

  • Nat Immunol. 2014 Mar;15(3):305.


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.

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