The localization and phenotype of muscularis macrophages. (Left panel) Anatomical overview of macrophage (Mφ) distribution in different layers of the gastrointestinal tract. (Upper right panel) Mφ (green, CX3CR1) located in the muscularis externa (MMφ) have a distinct morphology dependent on their position within circular and longitudinal muscle layers or myenteric plexus. MMφ in the myenteric plexus resemble microglia with a ramified, stellate shaped morphology and closely contact enteric neurons (red, TUBB3) and myenteric ganglia (blue, HUC/D). (Lower right panel) MMφ express typical Mφ-specific surface markers such as CX3CR1, CD64 and F4/80. They are characterized by their tissue-protective genetic signature, such as the expression of Arg1, Cd163, Ccl17, Retnla and Ald1a2. SmPlx = submucosal plexus. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)