Functional macrophages and gastrointestinal disorders

Figure 3 Functional role of macrophages in healthy or inflamed intestine. MΦ differentiate from blood Mo. Ly6c^lo Mo are proposed to be the precursors of resident MΦ. CD14^hiCD16^- Mo turn into resident or inflammatory MΦ according to different circumstances via the CCR2 pathway. In healthy intestine (left side), resident MΦ are F4/80^hi, class II MHC^hi CX3CR1^hi, CD11c⁺, CD103^- and Siglec F^-. They do not express high levels of costimulatory molecules such as CD40, CD80 and CD86. Their connections with CD4⁺/Foxp3⁺ T cells, IL-10 and TGF-β are helpful to maintain intestinal homeostasis (green arrows). GPBAR1 is essential to maintain intestinal immune homeostasis by regulating M₁/M₂ MΦ. In inflamed intestine (right side), Mo change into inflammatory MΦ, which produce TNF-β, IL-1, IL-6, IL-12, and IL-23, and activate effective T cells with several specific receptors, such as TLR, as well as induce respiratory burst (e.g., NO and H₂O₂ production), leading to inflammation (orange arrows). In addition, M₂ MΦ produce tissue-repairing factors such as VEGF, which shows a positive effect in individuals during inflammation (green arrow). Regarding MΦ and intestinal immunity, many details remain unclear - for instance, the functions of RoRy⁺ ILCs and CD200/200R (in blue rectangle) as well as that of Ly6C^hi/lo Mo. IL: Interleukin; ILC: Innate lymphoid cell; Mo: Monocytes; MΦ: Macrophages; NO: Nitric oxide; TGF: Tumor growth factor; TLR: Toll-like receptor; TNF: Tumor necrosis factor; VEGF: Vascular endothelial growth factor.