, the strongest genetic link to the development of Crohn's disease, was found to be expressed in fetal-like IECs following injury. Employing an ileal organoid model, we demonstrated that NOD2 activation by its peptidoglycan ligand potentiated an inflammatory gene signature characterized by interferon signaling, concurrent with enterocyte recovery. NOD2 deficiency exacerbated epithelial apoptosis following IR injury, whereas epithelial-specific NOD2 signaling promoted fetal-like IEC emergence and increased epithelial proliferation. Collectively, these findings reveal a pivotal role for the microbiota and NOD2-mediated microbial sensing in regulating fetal-like IEC fate after injury, thus contributing to the protective function of this microbial sensor during intestinal inflammation.
Tsang et al. (Tue,) studied this question.