Figure 1. Type 2 immune responses in the intestinal mucosa from healthy and inflammatory bowel disease (IBD).
Type 2 immune responses mediated by TH2 and ILC2 during homoeostatic conditions, inflammation and tissue repair: (a) At steady-state conditions, type 2 cytokines produced by either ILC2 or TH2 orchestrate epithelial homeostasis. Type 2 immune responses can promote crypt stemness and the epithelial cell differentiation towards the tuft and/or goblet cell lineage. This process is crucial to maintain a healthy mucus layer and eventually the integrity of the intestinal barrier. Epithelial cells derived alarmins (IL-25, CysLTs, IL-33, and TSLP) activate ILC2 promoting the establishment of tolerogenic immune responses. (b) In the inflamed intestine during IBD, ILC2, and TH2 accumulate in inflamed lesions. Damaged epithelium permeability and loss of the mucus layer might result in commensals bacterial translocation and dissemination. Dissemination of bacteria result in NOD2-dependent activation which results in the production of IL-33. Eventually, ILC2s are activated by IL-33 and in turn produce IL-5 and IL-13, which fuel chronic ileitis. (c) During the process of tissue repair, IL-4 or IL-13 combined with apoptotic cells stimulate macrophages to promote wound healing and tissue remodeling.