The PGD2–CRTH2 pathway counteracts the effect of Type 2 cytokines on the small intestinal epithelium during helminth infection. (1) Infection with intestinal helminth parasites elicits IL-13 production from ILC2s and other immune cell types that produce IL-13. (2) IL-13 acts on IL-13Rα1–expressing ISCs and other IECs, causing decreased proliferation, terminal differentiation, loss of Lgr5-expressing stem cells, goblet cell hyperplasia, and tuft cell hyperplasia. CRTH2 expression is also up-regulated. (3 and 4) Increased tuft cells are activated to produce PGD2 (3), which then acts back on CRTH2-expressing ISCs, and possibly other epithelial cell types that express CRTH2 (not depicted), to counteract the effects of IL-13 (4), increasing proliferation, suppressing goblet cell accumulation, and decreasing IL-13Rα1 expression.