Epithelial surfaces form critical barriers to the outside world and are continuously renewed by adult stem cells 1 . Whereas epithelial stem cell dynamics during homeostasis are increasingly well understood, how stem cells are redirected from a tissue-maintenance program to initiate repair after injury remains unclear. Here, we examined infection by Heligmosomoides polygyrus (Hp), a co-evolved pathosymbiont of mice, to assess the epithelial response to disruption of the mucosal barrier. Hp disrupts tissue integrity by penetrating the duodenal mucosa, where it develops while surrounded by a multicellular granulomatous infiltrate 2 . Unexpectedly, intestinal stem cell (ISC) markers, including Lgr5 3 , were lost in crypts overlying larvae-associated granulomas, despite continued epithelial proliferation. Granuloma-associated Lgr5 − crypt epithelia activated an interferon-gamma (IFNγ)-dependent transcriptional program, highlighted by Sca-1 expression, and IFNγ-producing immune cells were found in granulomas. A similar epithelial response accompanied systemic activation of immune cells, intestinal irradiation, or ablation of Lgr5 + ISCs. Granuloma-associated crypt cells generated fetal-like spheroids in culture, and a sub-population of Hp-induced cells activated a fetal-like transcriptional program, demonstrating that adult intestinal tissues can repurpose aspects of fetal development. Thus, re-initiation of the developmental program represents a fundamental mechanism by which the intestinal crypt can remodel to sustain function after injury.