Abstract

Subsets of innate lymphoid cells (ILCs) reside in the mucosa and regulate immune responses to external pathogens. While ILCs can be phenotypically classified into ILC1, ILC2 and ILC3 subsets, the transcriptional control of commitment to each ILC lineage is incompletely understood. Here we report that the transcription factor Runx3 was essential for the normal development of ILC1 and ILC3 cells but not of ILC2 cells. Runx3 controlled the survival of ILC1 cells but not of ILC3 cells. Runx3 was required for expression of the transcription factor RORγt and its downstream target, the transcription factor AHR, in ILC3 cells. The absence of Runx3 in ILCs exacerbated infection with Citrobacter rodentium. Therefore, our data establish Runx3 as a key transcription factor in the lineage-specific differentiation of ILC1 and ILC3 cells.

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Acknowledgements

We thank E. Vivier (Centre d'Immunologie de Marseille-Luminy) for NKp46-Cre mice; D.R. Littman (New York University) for Cbfbf/f, Runx3f/f and Runx3d+/YFP mice; S. Taffner for technical assistance; H. Miyoshi and A. Fuchs for technical advice; and D.K. Sojka, and S. Demehri for discussions. Supported by the Howard Hughes Medical Institute (W.M.Y.) and the US National Institutes of Health (R01AI097244 to T.Eg.; and T32-GM007200 for M.D.B.).

Author information

Affiliations

  1. Howard Hughes Medical Institute, Washington University School of Medicine, St. Louis, Missouri, USA.

    • Takashi Ebihara
    •  & Wayne M Yokoyama
  2. Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, USA.

    • Christina Song
    • , Stacy H Ryu
    • , Thaddeus S Stappenbeck
    • , Marco Colonna
    •  & Takeshi Egawa
  3. Division of Rheumatology, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, USA.

    • Beatrice Plougastel-Douglas
    • , Liping Yang
    • , Michael D Bern
    •  & Wayne M Yokoyama
  4. Department of Molecular Genetics, The Weizmann Institute of Science, Rehovot, Israel.

    • Ditsa Levanon
    •  & Yoram Groner
  5. Medical Scientist Training Program, Washington University School of Medicine, St. Louis, Missouri, USA.

    • Michael D Bern

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Contributions

T.Eb. and W.M.Y. designed experiments and analyzed data; T.Eb., C.S., S.H.R., B.P.-D., L.Y., M.D.B. and T.S.S. performed the experiments; D.L. and Y.G. supplied reagents; T.Eg. analyzed data obtained by chromatin immunoprecipitation followed by deep sequencing; and T.Eb., Y.G., T.S.S., M.C., T.Eg. and W.M.Y. wrote the paper.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Wayne M Yokoyama.

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https://doi.org/10.1038/ni.3272

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