CD64 distinguishes macrophages from dendritic cells in the gut and reveals the Th1‐inducing role of mesenteric lymph node macrophages during colitis

Dendritic cells ( DC s) and monocyte‐derived macrophages (MΦs) are key components of intestinal immunity. However, the lack of surface markers differentiating MΦs from DC s has hampered understanding of their respective functions. Here, we demonstrate that, using CD 64 expression, MΦs can be distinguished from DC s in the intestine of both mice and humans. On that basis, we revisit the phenotype of intestinal DC s in the absence of contaminating MΦs and we delineate a developmental pathway in the healthy intestine that leads from newly extravasated L y‐6 C hi monocytes to intestinal MΦs. We determine how inflammation impacts this pathway and show that T cell‐mediated colitis is associated with massive recruitment of monocytes to the intestine and the mesenteric lymph node ( MLN ). There, these monocytes differentiate into inflammatory MΦs endowed with phagocytic activity and the ability to produce inducible nitric oxide synthase. In the MLNs , inflammatory MΦs are located in the T ‐cell zone and trigger the induction of proinflammatory T cells. Finally, T cell‐mediated colitis develops irrespective of intestinal DC migration, an unexpected finding supporting an important role for MLN ‐resident inflammatory MΦs in the etiology of T cell‐mediated colitis.