Adaptation of innate lymphoid cells to a micronutrient deficiency promotes type 2 barrier immunity

Science. 2014 Jan 24;343(6169):432-7. doi: 10.1126/science.1247606.


How the immune system adapts to malnutrition to sustain immunity at barrier surfaces, such as the intestine, remains unclear. Vitamin A deficiency is one of the most common micronutrient deficiencies and is associated with profound defects in adaptive immunity. Here, we found that type 3 innate lymphoid cells (ILC3s) are severely diminished in vitamin A-deficient settings, which results in compromised immunity to acute bacterial infection. However, vitamin A deprivation paradoxically resulted in dramatic expansion of interleukin-13 (IL-13)-producing ILC2s and resistance to nematode infection in mice, which revealed that ILCs are primary sensors of dietary stress. Further, these data indicate that, during malnutrition, a switch to innate type 2 immunity may represent a powerful adaptation of the immune system to promote host survival in the face of ongoing barrier challenges.

Publication types

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

MeSH terms

  • Adaptive Immunity*
  • Animals
  • Citrobacter rodentium / immunology
  • Enterobacteriaceae Infections / immunology
  • Homeodomain Proteins / genetics
  • Immunity, Innate*
  • Interleukin-13 / biosynthesis
  • Lymphocytes / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Micronutrients / deficiency*
  • Vitamin A / immunology*
  • Vitamin A Deficiency / immunology*


  • Homeodomain Proteins
  • Interleukin-13
  • Micronutrients
  • Vitamin A
  • RAG-1 protein