Homeostatic Regulation of Intestinal Macrophages by the Transcription Factor IRF-2

Intestinal macrophages are crucial for maintaining mucosal immune homeostasis. However, the molecularmechanisms regulating their development remain largely unexplored. Here, I demonstrate that interferon regulatory factor 2 (IRF-2) is an essential transcription factor for intestinal macrophage homeostasis. Using IRF-2- deficient mice, I identified that IRF-2 is required for the maintenance of distinct colonic macrophage subsets.Notably, IRF-2 loss severely impaired CD4＋Tim4＋ macrophage development in a type I IFN-independent manner,whereas CD4＋Tim4－ subset exhibited a type I IFN-dependent defect, at least in part. These findings suggest that IRF-2 regulates macrophage development via both type I IFN-dependent and -independent mechanisms.This study provides novel insights into the transcriptional regulation of intestinal macrophages and their role in mucosal immunity. Shinshu Med J 73 : 223― 233, 2025