Trends Immunol. 2025 Dec 19:S1471-4906(25)00307-2. doi: 10.1016/j.it.2025.11.008. Online ahead of print.

ABSTRACT

Intestinal homeostasis is crucial for overall health, and its maintenance relies on a complex and delicate interplay between intestinal epithelial cells, the gut microbiota, and the immune system. Among immune components, group 3 innate lymphoid cells (ILC3s), which primarily reside in the intestinal microenvironment, play a crucial role in maintaining gut homeostasis. Through the expression of multiple effector molecules such as interleukin (IL)-22 and major histocompatibility complex class II (MHCII), ILC3s orchestrate intestinal epithelial responses and regulate innate and adaptive immunity, thereby collectively promoting a symbiotic host-microbiota relationship, supporting immune tolerance, and providing protection against pathogens. This review summarizes current understanding of ILC3 functions in gut homeostasis, highlights their interactions with the microbiota and other cell types, and outlines how aberrant ILC3 activity contributes to disease pathogenesis.

PMID:41421952 | DOI:10.1016/j.it.2025.11.008