Single-cell transcriptional analysis reveals ILC-like cells in zebrafish

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Science Immunology  16 Nov 2018:
Vol. 3, Issue 29, eaau5265
DOI: 10.1126/sciimmunol.aau5265

Fishing for ILCs in zebrafish

To date, most studies on innate lymphoid cells (ILCs) have been focused on their functions in mammals. It is well known that both lymphoid cells and adaptive immunity are not unique to mammals but are shared by all vertebrates. By studying lymphoid cells in rag1-deficient zebrafish that lack both B and T cells, Hernández et al. have examined the functions of ILC-like cells in zebrafish. Using single-cell RNA-seq to profile gene expression in gut-resident lymphocytes of rag1-deficient zebrafish after immune challenge, they have identified lymphocytes in zebrafish that correspond to mammalian ILC1, ILC2, and ILC3 lineages. Studying ILCs in zebrafish should lead to a better understanding of the evolutionary functions of ILCs.


Innate lymphoid cells (ILCs) are important mediators of the immune response and homeostasis in barrier tissues of mammals. However, the existence and function of ILCs in other vertebrates are poorly understood. Here, we use single-cell RNA sequencing to generate a comprehensive atlas of zebrafish lymphocytes during tissue homeostasis and after immune challenge. We profiled 14,080 individual cells from the gut of wild-type zebrafish, as well as of rag1-deficient zebrafish that lack T and B cells, and discovered populations of ILC-like cells. We uncovered a rorc-positive subset of ILCs that could express cytokines associated with type 1, 2, and 3 responses upon immune challenge. Specifically, these ILC-like cells expressed il22 and tnfa after exposure to inactivated bacteria or il13 after exposure to helminth extract. Cytokine-producing ILC-like cells express a specific repertoire of novel immune-type receptors, likely involved in recognition of environmental cues. We identified additional novel markers of zebrafish ILCs and generated a cloud repository for their in-depth exploration.

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