Mass Cytometry Reveals Innate Lymphoid Cell Differentiation Pathways in the Human Fetal Intestine

Innate lymphoid cells (ILCs) are abundant in mucosal tissues and involved in tissue homeostasis and barrier function. While several ILC subsets have been identified, it is unknown if additional heterogeneity exists and their differentiation pathways remain largely unclear. We applied mass cytometry to analyze ILCs in the human fetal intestine and distinguished 34 distinct clusters through a t-SNE-based analysis. A lineage (Lin)-CD7+CD127-CD45RO+CD56+ population clustered between the CD127+ ILC and natural killer (NK) cell subsets, and expressed diverse levels of Eomes, T-bet, GATA3 and RORγt. By visualizing the dynamics of the t-SNE computation, we identified smooth phenotypic transitions from cells within the LinCD7+CD127-CD45RO+CD56+ cluster to both the NK cells and CD127+ ILCs, revealing potential differentiation trajectories. In functional differentiation assays the LinCD7+CD127-CD45RO+CD56+ CD8a cells could develop into CD45RA+ NK cells and CD127+ RORγt+ ILC3-like cells. Thus, we identified a previously unknown intermediate innate subset that can differentiate into ILC3 and NK cells.

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@article{ bib:2018_exp_medicine,
    author = {Na Li and Vincent van Unen and Thomas H{\"o}llt and Allan Thompson and Jeroen van Bergen and Nicola Pezzotti and Elmar Eisemann and Anna Vilanova and Susana M. Chuva de Sousa Lopes and Boudewijn Lelieveldt and Frits Koning},
    title = { Mass Cytometry Reveals Innate Lymphoid Cell Differentiation Pathways in the Human Fetal Intestine },
    journal = { Journal of Experimental Medicine },
    number = { 5 },
    pages = { 1383 -- 1396 },
    year = { 2018 },
    doi = { 10.1084/jem.20171934 },
}