Figure 1. Upon barrier disruption or attachment of symbionts, APCs release inflammatory cytokines, including IL-23, in response to DAMPs and PAMPs at the site of damage.

IL-23 signaling leads to increased production of IL-22 and G-CSF by Th17 cells as well as increased differentiation of naïve cells into Th17 cells. Neutralization and microbial containment occur at the site of inflammation owing partially to increased antimicrobial peptides and neutrophil recruitment due to IL-22 and G-CSF signaling, respectively. Concurrently, loss of IL-17 receptors at the site of damage leads to loss of IL17R signaling and an increase in free IL-17. The increased free IL-17 works in a positive feedback loop to increase Th17 proliferation near the site of barrier disruption. IL17R signaling where receptors have not been damaged leads to stabilization of the transport protein PigR and increased sIgA transport to the lumen, allowing neutralization of overabundant microbes. Additionally, demonstrated T-cell receptor specificity for commensal microbes leads to increased activity of the Th17 cell type in response to intestinal microbial imbalances. APC, antigen-presenting cell; DAMP, damage-associated molecular pattern molecule; G-CSF, granulocyte-colony-stimulating factor; IL, interleukin; PAMP, pathogen-associated molecular pattern; Th, T helper.