Type 2 immunity is elicited during parasitic infection and contributes to the immunopathology of allergic diseases. Initiators of type 2 responses have attracted considerable debate. In the Journal of Experimental Medicine, Herbert and colleagues show that trefoil factor 2 (TFF2) is an early initiator of type 2 immunity in response to Nippostrongylus brasiliensis. Lung epithelial damage triggers release of TFF2. Asthmatic children have higher expression of TFF2. TFF2 signaling through the receptor CXCR4 leads to elaboration of the type 2–inducing cytokine interleukin 33 (IL-33); this promotes expression of IL-4, IL-13 and RELM-b, which are necessary for worm expulsion. TFF2-deficient mice have greater worm burdens and delayed type 2 immune responsiveness. These findings suggest that TFF2 contributes to the early type 2 immune response to parasites and aberrantly to asthma.

J. Exp. Med. (13 February 2012) doi:10.1084/jem.20110079