Immune subset-committed proliferating cells populate the human foetal intestine throughout the second trimester of gestation

Nannan Guo, Na Li, Li Jia, Qinyue Jiang, Mette Schreurs, Vincent Unen, Susana M. Chuva Sousa Lopes, Alexandra A. Vloemans, Jeroen Eggermont, Boudewijn Lelieveldt, Frank J. T. Staal, Noel F. C. C. Miranda, M. Fernanda Pascutti () and Frits Koning ()
Additional contact information
Nannan Guo: Leiden University Medical Center
Na Li: Leiden University Medical Center
Li Jia: Leiden University Medical Center
Qinyue Jiang: Leiden University Medical Center
Mette Schreurs: Leiden University Medical Center
Vincent Unen: Leiden University Medical Center
Susana M. Chuva Sousa Lopes: Leiden University Medical Center
Alexandra A. Vloemans: Leiden University Medical Center
Jeroen Eggermont: Leiden University Medical Center
Boudewijn Lelieveldt: Leiden University Medical Center
Frank J. T. Staal: Leiden University Medical Center
Noel F. C. C. Miranda: Leiden University Medical Center
M. Fernanda Pascutti: Leiden University Medical Center
Frits Koning: Leiden University Medical Center

Nature Communications, 2023, vol. 14, issue 1, 1-17

Abstract: Abstract The intestine represents the largest immune compartment in the human body, yet its development and organisation during human foetal development is largely unknown. Here we show the immune subset composition of this organ during development, by longitudinal spectral flow cytometry analysis of human foetal intestinal samples between 14 and 22 weeks of gestation. At 14 weeks, the foetal intestine is mainly populated by myeloid cells and three distinct CD3–CD7+ ILC, followed by rapid appearance of adaptive CD4+, CD8+ T and B cell subsets. Imaging mass cytometry identifies lymphoid follicles from week 16 onwards in a villus-like structure covered by epithelium and confirms the presence of Ki-67+ cells in situ within all CD3–CD7+ ILC, T, B and myeloid cell subsets. Foetal intestinal lymphoid subsets are capable of spontaneous proliferation in vitro. IL-7 mRNA is detected within both the lamina propria and the epithelium and IL-7 enhances proliferation of several subsets in vitro. Overall, these observations demonstrate the presence of immune subset-committed cells capable of local proliferation in the developing human foetal intestine, likely contributing to the development and growth of organized immune structures throughout most of the 2nd trimester, which might influence microbial colonization upon birth.

Date: 2023
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DOI: 10.1038/s41467-023-37052-4

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