Box 1. Conditions that may determine the outcome of IL-22 signaling in the intestine
Presence and expression of positive regulators
(AhR, IL-23, IL-1B, IL-7, Notch, butyrate).
Presence and expression of negative regulators
(IL-22BP, TGF-B, ICOS, c-Maf, IL-25 and IL-27, IL-10).
(local in small intestine or colon; or systemic).
Timing, duration and amount of IL-22 production.
Diseased versus homeostatic state (see Table 1 ).