Diet-dependent, microbiota-independent regulation of IL-10-producing lamina propria macrophages in the small intestine

Intestinal resident macrophages (M phi s) regulate gastrointestinal homeostasis via production of an anti-inflammatory cytokine interleukin (IL)-10. Although a constant replenishment by circulating monocytes is required to maintain the pool of resident M phi s in the colonic mucosa, the homeostatic regulation of M phi s in the small intestine (SI) remains unclear. Here, we demonstrate that direct stimulation by dietary amino acids regulates the homeostasis of intestinal M phi s in the SI. Mice that received total parenteral nutrition (TPN), which deprives the animals of enteral nutrients, displayed a significant decrease of IL-10-producing M phi s in the SI, whereas the IL-10-producing CD4(+) T cells remained intact. Likewise, enteral nutrient deprivation selectively affected the monocyte-derived F4/80(+) M phi population, but not non-monocytic precursor-derived CD103(+) dendritic cells. Notably, in contrast to colonic M phi s, the replenishment of SI Mfs and their IL-10 production were not regulated by the gut microbiota. Rather, SI M phi s were directly regulated by dietary amino acids. Collectively, our study highlights the dietdependent, microbiota-independent regulation of IL-10-producing resident M phi s in the SI.