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

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Hernández, Pedro P  ORCID logo
Strzelecka, Paulina M  ORCID logo
Athanasiadis, Emmanouil I  ORCID logo
Robalo, Ana F 

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.

Animals, Immunity, Innate, Lymphocytes, Single-Cell Analysis, Transcription, Genetic, Zebrafish
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Sci Immunol
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American Association for the Advancement of Science (AAAS)
Cancer Research Uk (None)
European Research Council (677501)
Medical Research Council (MC_PC_12009)
Medical Research Council (1942575)
The study was supported by Cancer Research UK grant number C45041/A14953 (to A.C. and E.I.A.), European Research Council project 677501 – ZF_Blood (to A.C. and P.M.S.), EMBO Long-Term Fellowship ALTF-807-2015 (to P.P.H), ANR grant 17-CE15-0017-01 – ZF-ILC (to P.P.H) and ANR-16-CE20-0002-03 (to J.-P.L), H2020-MSCA-IF-2015 grant 708128 – ZF-ILC (to P.P.H), ANR-10-LABX-73 (‘revive’ to P. Herbomel) and a core support grant from the Wellcome Trust and MRC to the Wellcome Trust – Medical Research Council Cambridge Stem Cell Institute.