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

## TL;DR

This study explores how innate lymphoid cells develop in the human fetus, showing they vary by tissue and may have tissue-specific origins.

## Contribution

The study identifies tissue-specific ILC progenitors in the fetal intestine, revealing distinct developmental patterns of ILC subsets during early human development.

## Key findings

- Fetal ILC subsets show distinct distribution and gene expression across tissues.
- CD34+RORγt+Eomes− and CD34+RORγt+Eomes+ cells are found in the fetal intestine.
- NK cells and ILC3s have unique developmental kinetics in different fetal tissues.

## Abstract

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.

CD16+ and CD16− Natural Killer cells and type 3 innate lymphoid cells are found in early human development with distinct distribution and phenotype across fetal tissues. The presence of CD34+RORyt+Eomes± cells selectively in the fetal intestine indicates the presence of tissue‐specific progenitors.