Figure 2. Homeostatic inhibition maintained by microbial regulation of mononuclear phagocytes.

At steady state, CS₃CR1⁺ MNPs (green) are able to extend trans-epithelial dendrites to sample luminal microbiota. Signals from luminal microbiota limit CS₃CR1⁺ MNP migration to MLN by way of Myd88 signaling (red line). In the setting of dysbiosis, CS₃CR1⁺ MNP can traffic luminal microbes to the MLN and promote pro-inflammatory immune responses. In the setting of barrier injury (indicated in pink), CS₃CR1⁺ MNPs expand from monocyte (Mo) precursors. Microbial signals support CS₃CR1⁺ MNP production of IL-23 and IL-1β which, subsequently, induce ILC3 production of IL-22 to promote mucosal healing and anti-microbial peptide production.