Development of the human fetal immune system: novel insights from high-dimensional single-cell technologies

Several studies have highlighted the uniqueness of the human immune system in early life. Due to the scarceness of human fetal tissues and technical limitations, a system-wide and detailed phenotypical characterization of the composition and development of the human fetal immune system was lacking. Here, I delineate the composition and development of the human fetal immune system using an array of advanced high-throughput technologies. First, mass cytometry analysis of the innate lymphoid cells revealed a previously unrecognized subset named int-ILC in the fetal intestine, which can give rise to NK cells and ILC3s. Moreover, by combining the acquired datasets from (imaging-) mass cytometry, single-cell RNA-sequencing and TCR sequencing with advanced computational analysis tools and functional analysis this revealed that memory-like CD4+ T cells were already generated in the developing human fetal intestine, indicative of in utero exposure to foreign antigens. Additionally, (imaging-) mass cytometry analysis of the immune cells in the fetal intestine, spleen and liver revealed an early-life immune compartmentalization in these different fetal tissues. Overall, our results deepens the understanding of prenatal immunity and may ultimately be useful for the development of “early” intervention strategies to prevent the development of immune mediated diseases later in life.LUMC / Geneeskunde Repositoriu