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

Jenny M Mjösberg; Sara Trifari; Natasha K Crellin; Charlotte P Peters; Cornelis M van Drunen; Berber Piet; Wytske J Fokkens; Tom Cupedo; Hergen Spits

doi:10.1038/ni.2104

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

Nat Immunol. 2011 Sep 11;12(11):1055-62. doi: 10.1038/ni.2104.

Authors

Jenny M Mjösberg¹, Sara Trifari, Natasha K Crellin, Charlotte P Peters, Cornelis M van Drunen, Berber Piet, Wytske J Fokkens, Tom Cupedo, Hergen Spits

Affiliation

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

PMID: 21909091
DOI: 10.1038/ni.2104

Abstract

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 (T(H)2) cytokines.

MeSH terms

Adult
Cell Differentiation
Cell Lineage
Cells, Cultured
Chronic Disease
Cytokines / immunology
Cytokines / metabolism*
Humans
Immunity, Innate*
Immunophenotyping
Interleukin-17 / immunology
Interleukin-17 / metabolism
Interleukin-33
Interleukins / immunology
Interleukins / metabolism
Intestines / pathology
Lymphocytes / immunology
Lymphocytes / metabolism*
Lymphocytes / pathology
NK Cell Lectin-Like Receptor Subfamily B / immunology
NK Cell Lectin-Like Receptor Subfamily B / metabolism*
Nasal Polyps
Receptors, Immunologic / immunology
Receptors, Immunologic / metabolism*
Receptors, Prostaglandin / immunology
Receptors, Prostaglandin / metabolism*
Rhinitis / immunology*
Rhinitis / pathology
Rhinitis / physiopathology
Sinusitis / immunology*
Sinusitis / pathology
Sinusitis / physiopathology
Th2 Cells / immunology
Th2 Cells / metabolism

Substances

Cytokines
IL25 protein, human
IL33 protein, human
Interleukin-17
Interleukin-33
Interleukins
NK Cell Lectin-Like Receptor Subfamily B
Receptors, Immunologic
Receptors, Prostaglandin
prostaglandin D2 receptor