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Human IL-25- and IL-33-responsive type 2 innate lymphoid cells are defined by expression of CRTH2 and CD161

Nature Immunology volume 12, pages 10551062 (2011) | Download Citation


Innate lymphoid cells (ILCs) are emerging as a family of effectors and regulators of innate immunity and tissue remodeling. Interleukin 22 (IL-22)- and IL-17-producing ILCs, which depend on the transcription factor RORγt, express CD127 (IL-7 receptor α-chain) and the natural killer cell marker CD161. Here we describe another lineage-negative CD127+CD161+ ILC population found in humans that expressed the chemoattractant receptor CRTH2. These cells responded in vitro to IL-2 plus IL-25 and IL-33 by producing IL-13. CRTH2+ ILCs were present in fetal and adult lung and gut. In fetal gut, these cells expressed IL-13 but not IL-17 or IL-22. There was enrichment for CRTH2+ ILCs in nasal polyps of chronic rhinosinusitis, a typical type 2 inflammatory disease. Our data identify a unique type of human ILC that provides an innate source of T helper type 2 (TH2) cytokines.

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We thank B. Hooibrink and J. Cupp and their teams for help with flow cytometry and Luminex assays; W. Ouyang and C. Kaplan for discussions; A. te Velde and C. Ponsioen for help with intestinal tissues; staff of the Bloemenhove clinic in Heemstede, the Netherlands, for fetal tissues; and K. Weijer, A. Voordouw, N. Legrand and B. Olivier for help with processing various tissues.

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Author notes

    • Sara Trifari
    •  & Natasha K Crellin

    Present address: La Jolla Institute for Allergy and Immunology, La Jolla, California, USA (S.T.), and Pfizer at Rinat, San Francisco, California, USA (N.K.C.).


  1. Tytgat Institute for Liver and Intestinal Research, University of Amsterdam, Amsterdam, The Netherlands.

    • Jenny M Mjösberg
    • , Charlotte P Peters
    •  & Hergen Spits
  2. Department of Immunology, Genentech, South San Francisco, California, USA.

    • Sara Trifari
    •  & Natasha K Crellin
  3. Department of Otorhinolaryngology, University of Amsterdam, Amsterdam, The Netherlands.

    • Cornelis M van Drunen
    •  & Wytske J Fokkens
  4. Department of Experimental Immunology and Pulmonology of the Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.

    • Berber Piet
  5. Department of Hematology, Erasmus University Medical Center, Rotterdam, The Netherlands.

    • Tom Cupedo


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J.M.M. designed the study, did experiments, analyzed the data and wrote the manuscript; S.T. designed the study, did experiments, analyzed the data and wrote the manuscript; N.K.C. did experiments and analyzed the data; C.P.P. did experiments, and provided and processed gut tissue; C.M.v.D. and W.J.F. provided inflamed and uninflamed nasal tissue; B.P. provided and processed lung tissue; T.C. designed the study; and H.S. designed the study and wrote the manuscript.

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The authors declare no competing financial interests.

Corresponding author

Correspondence to Hergen Spits.

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