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

The intestine is an important immunological organ in embryonic life, preparing the infant for the microbial colonization following birth. Here authors show that between gestational weeks 14 and 22, the human foetal intestine is first populated by myeloid and innate lymphoid cells, followed by the development of lymphoid cells and a wider range of proliferation-capable immune cell types. 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 2(nd) trimester, which might influence microbial colonization upon birth.

Automated summary

This study reveals the changes in immune subsets in the developing human foetal intestine, showing the sequential appearance of different types of immune cells between gestational weeks 14 and 22. The presence of immune subset-committed cells capable of local proliferation suggests their important role in the development of organized immune structures and potential influence on microbial colonization after birth.