Interleukin-12 and -23 Control Plasticity of CD127(+) Group 1 and Group 3 Innate Lymphoid Cells in the Intestinal Lamina Propria

Immunity. 2015 Jul 21;43(1):146-60. doi: 10.1016/j.immuni.2015.06.019. Epub 2015 Jul 14.


Human group 1 ILCs consist of at least three phenotypically distinct subsets, including NK cells, CD127(+) ILC1, and intraepithelial CD103(+) ILC1. In inflamed intestinal tissues from Crohn's disease patients, numbers of CD127(+) ILC1 increased at the cost of ILC3. Here we found that differentiation of ILC3 to CD127(+) ILC1 is reversible in vitro and in vivo. CD127(+) ILC1 differentiated to ILC3 in the presence of interleukin-2 (IL-2), IL-23, and IL-1β dependent on the transcription factor RORγt, and this process was enhanced in the presence of retinoic acid. Furthermore, we observed in resection specimen from Crohn's disease patients a higher proportion of CD14(+) dendritic cells (DC), which in vitro promoted polarization from ILC3 to CD127(+) ILC1. In contrast, CD14(-) DCs promoted differentiation from CD127(+) ILC1 toward ILC3. These observations suggest that environmental cues determine the composition, function, and phenotype of CD127(+) ILC1 and ILC3 in the gut.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation / immunology
  • Cells, Cultured
  • Crohn Disease / immunology
  • Dendritic Cells / immunology
  • Humans
  • Interleukin-12 Subunit p35 / immunology*
  • Interleukin-1beta / immunology
  • Interleukin-2 / immunology
  • Interleukin-23 Subunit p19 / immunology*
  • Interleukin-7 Receptor alpha Subunit / immunology*
  • Intestinal Mucosa / cytology
  • Intestinal Mucosa / immunology*
  • Killer Cells, Natural / immunology
  • Lipopolysaccharide Receptors / immunology
  • Lymphocyte Transfusion
  • Lymphocytes / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred NOD
  • Mice, Knockout
  • Mice, SCID
  • Nuclear Receptor Subfamily 1, Group F, Member 3 / immunology
  • Receptors, Retinoic Acid / metabolism
  • Retinoic Acid Receptor alpha
  • Retinoid X Receptor gamma / metabolism
  • Tretinoin / pharmacology


  • IL12A protein, human
  • IL1B protein, human
  • IL2 protein, human
  • IL23A protein, human
  • Interleukin-12 Subunit p35
  • Interleukin-1beta
  • Interleukin-2
  • Interleukin-23 Subunit p19
  • Interleukin-7 Receptor alpha Subunit
  • Lipopolysaccharide Receptors
  • Nuclear Receptor Subfamily 1, Group F, Member 3
  • RARA protein, human
  • RORC protein, human
  • Rara protein, mouse
  • Receptors, Retinoic Acid
  • Retinoic Acid Receptor alpha
  • Retinoid X Receptor gamma
  • retinoic acid receptor gamma
  • Tretinoin