Microbiota-Dependent Crosstalk Between Macrophages and ILC3 Promotes Intestinal Homeostasis

TLDR

The gut constantly encounters food antigens and microbes, making it a key site of immune tolerance where macrophages respond to microbiota signals by producing IL‑1. IL‑1 from macrophages activates intestinal ILC3s to secrete CSF‑2, which stimulates myeloid cells to produce retinoic acid and IL‑10, promoting regulatory T‑cell expansion and gut homeostasis.

Abstract

Gut Immune Tolerance With the constant assault of food antigens and its billions of resident microbes, the gut is an important site of immune tolerance. By studying specific intestinal immune cell populations in genetically modified mice, Mortha et al. ( 10.1126/science.1249288 , published online 13 March; see the Perspective by Aychek and Jung ) found that gut macrophages produce the cytokine interleukin-1 (IL-1) in response to signals derived from the microbiota. IL-1 acts on type 3 innate lymphoid cells in the intestine, which then produce the cytokine, colony-stimulating factor 2 (Csf2). Csf-2, in turn, induces myeloid cells (including dendritic cells and macrophages) to produce regulatory factors like retinoic acid and interleukin-10, which support the conversion and expansion of regulatory T cells, a population of cells known to be critical for maintaining immune tolerance in the gut.