Diet-mediated constitutive induction of novel IL-4+ ILC2 cells maintains intestinal homeostasis in mice

J Exp Med. 2023 Aug 7;220(8):e20221773. doi: 10.1084/jem.20221773. Epub 2023 May 10.

Abstract

Group 2 innate lymphoid cells (ILC2s) expressing IL-5 and IL-13 are localized at various mucosal tissues and play critical roles in the induction of type 2 inflammation, response to helminth infection, and tissue repair. Here, we reveal a unique ILC2 subset in the mouse intestine that constitutively expresses IL-4 together with GATA3, ST2, KLRG1, IL-17RB, and IL-5. In this subset, IL-4 expression is regulated by mechanisms similar to but distinct from those observed in T cells and is partly affected by IL-25 signaling. Although the absence of the microbiota had marginal effects, feeding mice with a vitamin B1-deficient diet compromised the number of intestinal IL-4+ ILC2s. The decrease in the number of IL-4+ ILC2s caused by the vitamin B1 deficiency was accompanied by a reduction in IL-25-producing tuft cells. Our findings reveal that dietary vitamin B1 plays a critical role in maintaining interaction between tuft cells and IL-4+ ILC2s, a previously uncharacterized immune cell population that may contribute to maintaining intestinal homeostasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Diet*
  • Gastrointestinal Microbiome
  • Interleukin-4 / metabolism
  • Intestinal Mucosa* / cytology
  • Intestinal Mucosa* / immunology
  • Mice
  • Mice, Inbred C57BL
  • Organoids / cytology
  • Organoids / immunology
  • Specific Pathogen-Free Organisms
  • Thiamine* / metabolism
  • Trinitrobenzenesulfonic Acid

Substances

  • Thiamine
  • Mydgf protein, mouse
  • Interleukin-4
  • Trinitrobenzenesulfonic Acid