IL-15 sustains IL-7R-independent ILC2 and ILC3 development

Nat Commun. 2017 Mar 31:8:14601. doi: 10.1038/ncomms14601.

Abstract

The signals that maintain tissue-resident innate lymphoid cells (ILC) in different microenvironments are incompletely understood. Here we show that IL-7 receptor (IL-7R) is not strictly required for the development of any ILC subset, as residual cells persist in the small intestinal lamina propria (siLP) of adult and neonatal Il7ra-/- mice. Il7ra-/- ILC2 primarily express an ST2- phenotype, but are not inflammatory ILC2. CCR6+ ILC3, which express higher Bcl-2 than other ILC3, are the most abundant subset in Il7ra-/- siLP. All ILC subsets are functionally competent in vitro, and are sufficient to provide enhanced protection to infection with C. rodentium. IL-15 equally sustains wild-type and Il7ra-/- ILC survival in vitro and compensates for IL-7R deficiency, as residual ILCs are depleted in mice lacking both molecules. Collectively, these data demonstrate that siLP ILCs are not completely IL-7R dependent, but can persist partially through IL-15 signalling.

Publication types

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

MeSH terms

  • Animals
  • Female
  • Immunity, Innate
  • Interleukin-15 / genetics
  • Interleukin-15 / immunology*
  • Intestine, Small / immunology
  • Killer Cells, Natural / immunology
  • Lymphocyte Subsets / immunology*
  • Lymphocytes / immunology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mucous Membrane / immunology
  • Receptors, Interleukin-7 / genetics
  • Receptors, Interleukin-7 / immunology*
  • Signal Transduction

Substances

  • Interleukin-15
  • Receptors, Interleukin-7