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Human type 1 innate lymphoid cells accumulate in inflamed mucosal tissues

Abstract

Innate lymphoid cells (ILCs) are effectors of innate immunity and regulators of tissue modeling. Recently identified ILC populations have a cytokine expression pattern that resembles that of the helper T cell subsets TH2, TH17 and TH22. Here we describe a distinct ILC subset similar to TH1 cells, which we call 'ILC1'. ILC1 cells expressed the transcription factor T-bet and responded to interleukin 12 (IL-12) by producing interferon-γ (IFN-γ). ILC1 cells were distinct from natural killer (NK) cells as they lacked perforin, granzyme B and the NK cell markers CD56, CD16 and CD94, and could develop from RORγt+ ILC3 under the influence of IL-12. The frequency of the ILC1 subset was much higher in inflamed intestine of people with Crohn's disease, which indicated a role for these IFN-γ-producing ILC1 cells in the pathogenesis of gut mucosal inflammation.

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Figure 1: Phenotypes and gene-expression profiles of ILC populations in human tonsil.
Figure 2: The c-KitNKp44 ILCs have characteristics of TH1 cells.
Figure 3: ILC1 cells are distinct from mature NK cells.
Figure 4: Stable cell lines can be generated from the ILC1 subset.
Figure 5: Accumulation of ILC1 cells in inflamed intestine of people with Crohn's disease.
Figure 6: Expansion of the ILC1 subset during gut inflammation in NSG mice reconstituted with fetal human HSCs (CD34+CD38).
Figure 7: IL-12 induces ILC1 differentiation.
Figure 8: RORγt+ ILCs of fetal gut are able to differentiate into ILC1.

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Acknowledgements

We thank B. Hooibrink for help with flow cytometry; staff of the Bloemenhove clinic in Heemstede, the Netherlands, for fetal tissues; A. Voordouw for processing fetal material; and W. Fokkens and C. van Drunen (Academic Medical Center, University of Amsterdam) for providing human tonsils.

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Authors

Contributions

J.H.B. designed the study, did experiments, analyzed data and wrote the manuscript; C.P.P. designed the study, did experiments and analyzed data; M.M. did experiments; A.A.t.V. provided gut tissue; S.L.M. performed the histopathological analysis; K.W. provided fetal gut tissue and HIS-mice; H.S.H. did experiments; S.E.H. did experiments; N.L. helped with HIS mice; C.J.B. and W.A.B. provided surgical resection specimen tissue; J.M.M. designed the study, did experiments and analyzed data; H.S. designed the study, analyzed data and wrote the manuscript.

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Correspondence to Hergen Spits.

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The authors declare no competing financial interests.

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Bernink, J., Peters, C., Munneke, M. et al. Human type 1 innate lymphoid cells accumulate in inflamed mucosal tissues. Nat Immunol 14, 221–229 (2013). https://doi.org/10.1038/ni.2534

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