Although the fetal immune system is considered tolerogenic, preterm infants can suffer from severe intestinal inflammation, including necrotizing enterocolitis (NEC). Here, we demonstrate that human fetal intestines predominantly contain tumor necrosis factor-a (TNF-a) + CD4 + CD69 + T effector memory (Tem) cells. Single-cell RNA sequencing of fetal intestinal CD4 + T cells showed a T helper 1 phenotype and expression of genes mediating epithelial growth and cell cycling. Organoid co-cultures revealed a dosedependent, TNF-a-mediated effect of fetal intestinal CD4 + T cells on intestinal stem cell (ISC) development, in which low T cell numbers supported epithelial development, whereas high numbers abrogated ISC proliferation. CD4 + Tem cell frequencies were higher in inflamed intestines from preterm infants with NEC than in healthy infant intestines and showed enhanced TNF signaling. These findings reveal a distinct population of TNF-a-producing CD4 + T cells that promote mucosal development in fetal intestines but can also mediate inflammation upon preterm birth.

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Background/Aims: A temporary loop ileostomy is constructed to protect a distal colonic anastomosis. Closure is usually performed not earlier than 8–12 weeks after the primary operation. During this period, stoma-related complications can occur and enhance the adverse effect on quality of life. The aim of this study was to evaluate the length of time between ileostomy construction and closure, to quantify stoma-related morbidity and to examine the potential advantages of early ileostomy closure. Methods: Sixty-nine patients with a temporary, protective loop ileostomy (constructed between January 1996 and December 2000) were retrospectively analysed. The analysis was done by reviewing the medical records and the notes of the stoma care nurse. Results: Sixty ileostomies (87%) were closed after a median period of 24 weeks (range 2–124 weeks). Stoma-related complications occurred in 29 of the 69 patients (42%), and 11 patients (18%) had complications after ileostomy closure. Conclusion: The length of time between ileostomy construction and closure was substantially longer than initially planned. Earlier ileostomy closure (preferably even during the initial admission) could reduce the frequently occurring stoma-related morbidity in these patients and thus improve quality of life.

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