Human type 1 innate lymphoid cells accumulate in inflamed mucosal tissues

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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.

Author information

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.

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) doi:10.1038/ni.2534

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