A Novel Role For IL-13 in Enteric Infections and Allergy

IL-13 driven goblet cell (GC) hyperplasia and mucus hyper-secretion are characteristic of intestinal helminth infections and allergic responses. How IL-13 contributes to these processes is largely unknown.  Intestinal GCs can form goblet cell associated antigen passages (GAPs) delivering luminal antigens to lamina propria dendritic cells (DCs) to shape gut immune responses. GAP formation occurs spontaneously in the small intestine in response to acetylcholine, but not in the colon where it is inhibited by the microbiota. We observed that IL-13 induced GAPs in the small intestine and colon by mechanisms independent of acetylcholine.  IL-13 induced GAPs within 30 min of administration, and the effect lasted for 48h. The prolonged induction of IL-13 induced GAP formation resulted in increased luminal antigen delivery to lamina propria DCs as assessed by their ability to induced T cell proliferation. In contrast to GAP formation in response to acetylcholine, IL-13 induced GAPs were mediated via activation of CD38 and the downstream ADP ribose pathway.  Here we describe that a cytokine associated with enteric infections and allergy, promotes trans-epithelial delivery of luminal antigens to induce immune responses.  This function of IL-13 could play a central role in responses to helminths and allergic responses