iScience (Jun 2024)
Pro-inflammatory T cells-derived cytokines enhance the maturation of the human fetal intestinal epithelial barrier
- Francesca P. Giugliano,
- Marit Navis,
- Sarah Ouahoud,
- Tânia Martins Garcia,
- Irini A.M. Kreulen,
- Evelina Ferrantelli,
- Sander Meisner,
- Jacqueline L.M. Vermeulen,
- Manon van Roest,
- Jean-Noël Billaud,
- Jan Koster,
- Yousif Dawood,
- Bernadette S. de Bakker,
- Daisy I. Picavet-Havik,
- Irene M. Schimmel,
- Nicole N. van der Wel,
- Pim J. Koelink,
- Manon E. Wildenberg,
- Joep P.M. Derikx,
- Wouter J. de Jonge,
- Ingrid B. Renes,
- Ruurd M. van Elburg,
- Vanesa Muncan
Affiliations
- Francesca P. Giugliano
- Department of Gastroenterology and Hepatology, Tytgat Institute for Liver and Intestinal Research, Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam University Medical Center (AUMC), University of Amsterdam, Amsterdam, the Netherlands
- Marit Navis
- Department of Gastroenterology and Hepatology, Tytgat Institute for Liver and Intestinal Research, Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam University Medical Center (AUMC), University of Amsterdam, Amsterdam, the Netherlands
- Sarah Ouahoud
- Department of Gastroenterology and Hepatology, Tytgat Institute for Liver and Intestinal Research, Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam University Medical Center (AUMC), University of Amsterdam, Amsterdam, the Netherlands
- Tânia Martins Garcia
- Department of Gastroenterology and Hepatology, Tytgat Institute for Liver and Intestinal Research, Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam University Medical Center (AUMC), University of Amsterdam, Amsterdam, the Netherlands
- Irini A.M. Kreulen
- Department of Gastroenterology and Hepatology, Tytgat Institute for Liver and Intestinal Research, Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam University Medical Center (AUMC), University of Amsterdam, Amsterdam, the Netherlands
- Evelina Ferrantelli
- Department of Gastroenterology and Hepatology, Tytgat Institute for Liver and Intestinal Research, Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam University Medical Center (AUMC), University of Amsterdam, Amsterdam, the Netherlands
- Sander Meisner
- Department of Gastroenterology and Hepatology, Tytgat Institute for Liver and Intestinal Research, Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam University Medical Center (AUMC), University of Amsterdam, Amsterdam, the Netherlands
- Jacqueline L.M. Vermeulen
- Department of Gastroenterology and Hepatology, Tytgat Institute for Liver and Intestinal Research, Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam University Medical Center (AUMC), University of Amsterdam, Amsterdam, the Netherlands
- Manon van Roest
- Department of Gastroenterology and Hepatology, Tytgat Institute for Liver and Intestinal Research, Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam University Medical Center (AUMC), University of Amsterdam, Amsterdam, the Netherlands
- Jean-Noël Billaud
- QIAGEN Digital Insights, 1001 Marshall Street, Redwood City, CA, USA; DNAnexus, 204 El Camino Real, Mountain View, CA, USA
- Jan Koster
- Center for Experimental and Molecular Medicine (CEMM), Amsterdam University Medical Center (AUMC), University of Amsterdam, Amsterdam, the Netherlands
- Yousif Dawood
- Department of Obstetrics and Gynecology, Amsterdam University Medical Center (AUMC), University of Amsterdam, Amsterdam, the Netherlands; Amsterdam Reproduction and Development research institute, Amsterdam University Medical Center (AUMC), University of Amsterdam, Amsterdam, the Netherlands
- Bernadette S. de Bakker
- Department of Obstetrics and Gynecology, Amsterdam University Medical Center (AUMC), University of Amsterdam, Amsterdam, the Netherlands; Amsterdam Reproduction and Development research institute, Amsterdam University Medical Center (AUMC), University of Amsterdam, Amsterdam, the Netherlands
- Daisy I. Picavet-Havik
- Department of Medical Biology, Electron Microscopy Center Amsterdam, Amsterdam University Medical Center (AUMC), University of Amsterdam, Amsterdam, the Netherlands
- Irene M. Schimmel
- Department of Medical Biology, Electron Microscopy Center Amsterdam, Amsterdam University Medical Center (AUMC), University of Amsterdam, Amsterdam, the Netherlands
- Nicole N. van der Wel
- Department of Medical Biology, Electron Microscopy Center Amsterdam, Amsterdam University Medical Center (AUMC), University of Amsterdam, Amsterdam, the Netherlands
- Pim J. Koelink
- Department of Gastroenterology and Hepatology, Tytgat Institute for Liver and Intestinal Research, Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam University Medical Center (AUMC), University of Amsterdam, Amsterdam, the Netherlands
- Manon E. Wildenberg
- Department of Gastroenterology and Hepatology, Tytgat Institute for Liver and Intestinal Research, Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam University Medical Center (AUMC), University of Amsterdam, Amsterdam, the Netherlands
- Joep P.M. Derikx
- Department of Pediatric Surgery, Pediatric Surgery Center of Amsterdam, Amsterdam University Medical Center (AUMC), University of Amsterdam, Amsterdam, the Netherlands
- Wouter J. de Jonge
- Department of Gastroenterology and Hepatology, Tytgat Institute for Liver and Intestinal Research, Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam University Medical Center (AUMC), University of Amsterdam, Amsterdam, the Netherlands
- Ingrid B. Renes
- Department of Pediatrics, Amsterdam University Medical Center (AUMC), Emma Children’s Hospital, Amsterdam, the Netherlands; Danone Nutricia Research, Utrecht, the Netherlands
- Ruurd M. van Elburg
- Department of Pediatrics, Amsterdam University Medical Center (AUMC), Emma Children’s Hospital, Amsterdam, the Netherlands
- Vanesa Muncan
- Department of Gastroenterology and Hepatology, Tytgat Institute for Liver and Intestinal Research, Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam University Medical Center (AUMC), University of Amsterdam, Amsterdam, the Netherlands; Corresponding author
- Journal volume & issue
-
Vol. 27,
no. 6
p. 109909
Abstract
Summary: 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.
