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Transcriptional regulation of innate lymphoid cell fate

Nature Reviews Immunology volume 15, pages 415–428 (2015)Cite this article

Subjects

Key Points

  • Three distinct groups of innate lymphoid cells (ILCs) have been categorized — these have unique and overlapping functions in immunity.

  • Several committed ILC-restricted progenitor subsets have been discovered, and the transcriptional programmes that drive their generation have also been deciphered.

  • A complex repertoire of transcription factors has been shown to control ILC diversification and maturation.

  • ILC subsets within tissues are maintained and tuned through a set of environmental signals that balance cellular homeostasis and functional plasticity.

Abstract

Innate lymphoid cells (ILCs) are a recently described family of lymphoid effector cells that have important roles in immune defence, inflammation and tissue remodelling. It has been proposed that ILCs represent 'innate' homologues of differentiated effector T cells, and they have been categorized into three groups — namely, ILC1s, ILC2s and ILC3s — on the basis of their expression of cytokines and transcription factors that are typically associated with T helper 1 (TH1)-, TH2- and TH17-type immune responses, respectively. Indeed, remarkable similarity is seen between the specific transcription factors required for the development and diversification of different ILC groups and those that drive effector T cell differentiation. The recent identification of dedicated ILC precursors has provided a view of the mechanisms that control this first essential stage of ILC development. Here, we discuss the transcriptional mechanisms that regulate ILC development and diversification into distinct effector subsets with key roles in immunity and tissue homeostasis. We further caution against the current distinction between 'helper' versus 'killer' subsets in the evolving area of ILC nomenclature.

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Figure 1: ILC groups and subsets.
Figure 2: Model for mouse ILC development.
Figure 3: Models for ILC lineage commitment.
Figure 4: ILC maintenance and plasticity in tissues.

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Acknowledgements

The authors would like to thank all members of the laboratory for helpful discussions. This work is supported by grants from the Institut Pasteur, Institut National de la Santé et de la Recherche Médicale (INSERM), Ligue National Contre le Cancer and the Agence National pour la Recherche. The authors apologize to those colleagues whose work has not been cited owing to space constraints.

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  1. Innate Immunity Unit, Institut Pasteur, Paris 75015, and the Institut National de la Santé et de la Recherche Médicale (INSERM) U668, Paris 75015, France.,

    Nicolas Serafini, Christian A. J. Vosshenrich & James P. Di Santo

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  1. Nicolas Serafini
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  3. James P. Di Santo
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Correspondence to James P. Di Santo.

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James P. Di Santo is a founder and stakeholder in AXENIS (Paris, France).

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Serafini, N., Vosshenrich, C. & Di Santo, J. Transcriptional regulation of innate lymphoid cell fate. Nat Rev Immunol 15, 415–428 (2015). https://doi.org/10.1038/nri3855

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