IL-25-responsive, lineage-negative KLRG1(hi) cells are multipotential 'inflammatory' type 2 innate lymphoid cells

Nat Immunol. 2015 Feb;16(2):161-9. doi: 10.1038/ni.3078. Epub 2014 Dec 22.


Innate lymphoid cells (ILCs) are lymphocyte-like cells that lack T cell or B cell antigen receptors and mediate protective and repair functions through cytokine secretion. Among these, type 2 ILCs (ILC2 cells) are able to produce type 2 cytokines. We report the existence of an inflammatory ILC2 (iILC2) population responsive to interleukin 25 (IL-25) that complemented IL-33-responsive natural ILC2 (nILC2) cells. iILC2 cells developed into nILC2-like cells in vitro and in vivo and contributed to the expulsion of Nippostrongylus brasiliensis. They also acquired IL-17-producing ability and provided partial protection against Candida albicans. We propose that iILC2 cells are transient progenitors of ILCs mobilized by inflammation and infection that develop into nILC2-like cells or ILC3-like cells and contribute to immunity to both helminths and fungi.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Candida albicans / immunology
  • Candidiasis / immunology
  • Cell Lineage
  • Gene Deletion
  • Inflammation / immunology
  • Interleukin-17 / metabolism*
  • Lectins, C-Type
  • Leukocytes / immunology
  • Lung / immunology
  • Lung / pathology
  • Lymphocytes / cytology
  • Lymphocytes / immunology*
  • Mice
  • Nippostrongylus / immunology
  • Receptors, Immunologic / genetics
  • Receptors, Immunologic / metabolism*
  • Receptors, Interleukin-7 / metabolism
  • Strongylida Infections / immunology


  • Interleukin-17
  • Klrg1 protein, mouse
  • Lectins, C-Type
  • Receptors, Immunologic
  • Receptors, Interleukin-7