iScience · 2024
Pro-inflammatory T cells-derived cytokines enhance the maturation of the human fetal intestinal epithelial barrier.
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Giugliano Francesca P, Navis Marit, Ouahoud Sarah, Garcia Tânia Martins, Kreulen Irini A M, Ferrantelli Evelina, Meisner Sander, Vermeulen Jacqueline L M, van Roest Manon, Billaud Jean-Noël, Koster Jan, Dawood Yousif, de Bakker Bernadette S, Picavet-Havik Daisy I, Schimmel Irene M, van der Wel Nicole N, Koelink Pim J, Wildenberg Manon E, Derikx Joep P M, de Jonge Wouter J, Renes Ingrid B, van Elburg Ruurd M, Muncan Vanesa
Аннотация
Small intestine (SI) maturation during early life is pivotal in preventing the onset of gut diseases. In this study we interrogated the milestones of SI development by gene expression profiling and ingenuity pathway analyses. We identified a set of cytokines as main regulators of changes observed across different developmental stages. Upon cytokines stimulation, with IFNγ as the most contributing factor, human fetal organoids (HFOs) increase brush border gene expression and enzyme activity as well as trans-epithelial electrical resistance. Electron microscopy revealed developed brush border and loss of fetal cell characteristics in HFOs upon cytokine stimulation. We identified T cells as major source of IFNγ production in the fetal SI lamina propria. Co-culture of HFOs with T cells recapitulated the major effects of cytokine stimulation. Our findings underline pro-inflammatory cytokines derived from T cells as pivotal factors inducing functional SI maturation in vivo and capable of modulating the barrier maturation of HFOs in vitro.