Renée R C E Schreurs, Martin E Baumdick, Adrian F Sagebiel, Max Kaufmann, Michal Mokry, Paul L Klarenbeek, Nicola Schaltenberg, Fenja L Steinert, Jorik M van Rijn, Agata Drewniak, Sarah-May M L The, Roel Bakx, Joep P M Derikx, Niek de Vries, Willemijn E Corpeleijn, Steven T Pals, Nicola Gagliani, Manuel A Friese, Sabine Middendorp, Edward E S Nieuwenhuis, Konrad Reinshagen, Teunis B H Geijtenbeek, Johannes B van Goudoever, Madeleine J Bunders
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-α (TNF-α)+ 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 dose-dependent, TNF-α-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...
February 5, 2019: Immunity