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Notch signaling is necessary for adult, but not fetal, development of RORγt+ innate lymphoid cells

Nature Immunology volume 12, pages 949–958 (2011)Cite this article

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Abstract

The transcription factor RORγt is required for the development of several innate lymphoid populations, such as lymphoid tissue–inducer cells (LTi cells) and cells that secrete interleukin 17 (IL-17) or IL-22. The progenitor cells as well as the developmental stages that lead to the emergence of RORγt+ innate lymphoid cells (ILCs) remain undefined. Here we identify the chemokine receptor CXCR6 as an additional marker of the development of ILCs and show that common lymphoid progenitors lost B cell and T cell potential as they successively acquired expression of the integrin α4β7 and CXCR6. Whereas fetal RORγt+ cells matured in the fetal liver environment, adult bone marrow–derived RORγt+ ILCs matured outside the bone marrow, in a Notch2-dependent manner. Therefore, fetal and adult environments influence the differentiation of RORγt+ cells differently.

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Figure 1: Fetal liver RORγt+ cells differentiate from CLPs.
Figure 2: Expression of α4β7 and CXCR6 defines two steps during differentiation into RORγt+ cells.
Figure 3: Both progenitors and mature cells migrate from the fetal liver to the periphery.
Figure 4: Bone marrow CLPs are the progenitors of adult RORγt+ cells.
Figure 5: The expression of α4β7 and CXCR6 defines bone marrow CLP subsets.
Figure 6: Peripheral CLP-like populations are the source of adult RORγt+ cells.
Figure 7: The Notch pathway is required for the differentiation of adult RORγt+ cells.

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  • 23 September 2011

    In the version of this article initially published, some labels in Figures 1 and 7, text on pages 950, 951, 956 and 957 and figure citations on page 952 were incorrect. In Figure 1c, bottom left, the middle label should be CD3-CXCR6+; in Figure 7a,b, the vertical axis label for the second column should be IL-7Rα and for the third column should be CD19; and in Figure 7d, the horizontal axis should include one arrow per column and the arrows for the middle and right columns should be labeled RORγt. On page 950, left column, the phrase "at double-negative state 3" should be deleted; on page 951, right column, penultimate line, the third genotype should be Cxcr6GFP/GFP; the legend to Figure 7a,b should read "...cells plated on OP9-DL4 stroma"; and on page 957, column 1, paragraph 2, the second sentence should end "...cells on OP9 cells." On page 952, right column, line 1, the first citation "(Fig. 3b)" should read "(data not shown)"; and on line 7, the citation "(Fig. 3e)" should read "(Fig. 3b)." The errors have been corrected in the HTML and PDF versions of the article.

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Acknowledgements

We thank J. Bertrand and R. Lo Man for comments on the manuscript; F. Geissmann (King's College London) for Cxcr6GFP/+ mice; and S. Ezine (Institut National de la Santé et de la Recherche Médicale U591) for nude mice. Supported by the Ministère de la Recherche (C.P.), Association pour la Recherche sur le Cancer (C.P.), Swiss National Science Foundation (S.S.), Fondation Santé (S.S.), Institut Pasteur (A.C., L.B. and A.L.), Université Paris Diderot (R.G., C.P. and S.C.), Institut National de la Santé et de la Recherche Médicale (A.C.) and Agence Nationale de Recherches (A.C., R.G. and S.S.).

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Authors and Affiliations

  1. Institut Pasteur, Unité de Lymphopoièse, Paris, France

    Cécilie Possot, Sandrine Schmutz, Sylvestre Chea, Laurent Boucontet, Ana Cumano & Rachel Golub

  2. L'Université Paris Diderot, Sorbonne Paris Cité (Cellule Pasteur), Paris, France

    Cécilie Possot, Sylvestre Chea & Rachel Golub

  3. Institut National de la Santé et de la Recherche Médicale U668, Paris, France

    Cécilie Possot, Sandrine Schmutz, Sylvestre Chea, Laurent Boucontet, Ana Cumano & Rachel Golub

  4. Institut Pasteur, Plate Forme de Cytometrie, Paris, France

    Anne Louise

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Contributions

C.P. and R.G. designed the experiments; C.P. and S.S. did the experiments with assistance from L.B. for quantitative RT-PCR, S.C. for supplementary figures, and A.L. for cell sorting; and C.P. and R.G. analyzed the data and wrote the manuscript with contributions from A.C.

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Correspondence to Rachel Golub.

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Possot, C., Schmutz, S., Chea, S. et al. Notch signaling is necessary for adult, but not fetal, development of RORγt+ innate lymphoid cells. Nat Immunol 12, 949–958 (2011). https://doi.org/10.1038/ni.2105

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