Distinct Tissue-Dependent Composition and Gene Expression of Human Fetal Innate Lymphoid Cells

The human fetal immune system starts to develop in the first trimester and likely plays a crucial role in fetal development and maternal-fetal tolerance. Innate lymphoid cells (ILCs) are the earliest lymphoid cells to arise in the human fetus. ILCs consist of natural killer (NK) cells, ILC1s, ILC2s, and ILC3s that all share a common lymphoid origin. Here, we studied fetal ILC subsets, mainly NK cells and ILC3s and their potential progenitors, across human fetal tissues. Our results show that fetal ILC subsets have distinct distribution, developmental kinetics, and gene expression profiles across human fetal tissues. Furthermore, we identify CD34⁺RORγt⁺Eomes^- and CD34⁺RORγt⁺Eomes⁺ cells in the fetal intestine, indicating that tissue-specific ILC progenitors exist already during fetal development.