TY - JOUR
T1 - Pro-inflammatory T cells-derived cytokines enhance the maturation of the human fetal intestinal epithelial barrier
AU - Giugliano, Francesca P.
AU - Navis, Marit
AU - Ouahoud, Sarah
AU - Garcia, Tânia Martins
AU - Kreulen, Irini A.M.
AU - Ferrantelli, Evelina
AU - Meisner, Sander
AU - Vermeulen, Jacqueline L.M.
AU - van Roest, Manon
AU - Billaud, Jean Noël
AU - Koster, Jan
AU - Dawood, Yousif
AU - de Bakker, Bernadette S.
AU - Picavet-Havik, Daisy I.
AU - Schimmel, Irene M.
AU - van der Wel, Nicole N.
AU - Koelink, Pim J.
AU - Wildenberg, Manon E.
AU - Derikx, Joep P.M.
AU - de Jonge, Wouter J.
AU - Renes, Ingrid B.
AU - van Elburg, Ruurd M.
AU - Muncan, Vanesa
N1 - Publisher Copyright: © 2024 The Authors
PY - 2024/6/21
Y1 - 2024/6/21
N2 - 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.
AB - 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.
KW - Cell biology
KW - Developmental biology
KW - Immunology
UR - http://www.scopus.com/inward/record.url?scp=85193451388&partnerID=8YFLogxK
U2 - 10.1016/j.isci.2024.109909
DO - 10.1016/j.isci.2024.109909
M3 - Article
C2 - 38812539
SN - 2589-0042
VL - 27
JO - iScience
JF - iScience
IS - 6
M1 - 109909
ER -