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
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Adult
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Cell Differentiation
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Cell Lineage
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Cells, Cultured
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Chronic Disease
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Cytokines / immunology
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Cytokines / metabolism*
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Humans
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Immunity, Innate*
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Immunophenotyping
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Interleukin-17 / immunology
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Interleukin-17 / metabolism
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Interleukin-33
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Interleukins / immunology
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Interleukins / metabolism
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Intestines / pathology
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Lymphocytes / immunology
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Lymphocytes / metabolism*
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Lymphocytes / pathology
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NK Cell Lectin-Like Receptor Subfamily B / immunology
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NK Cell Lectin-Like Receptor Subfamily B / metabolism*
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Nasal Polyps
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Receptors, Immunologic / immunology
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Receptors, Immunologic / metabolism*
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Receptors, Prostaglandin / immunology
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Receptors, Prostaglandin / metabolism*
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Rhinitis / immunology*
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Rhinitis / pathology
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Rhinitis / physiopathology
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Sinusitis / immunology*
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Sinusitis / pathology
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Sinusitis / physiopathology
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Th2 Cells / immunology
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Th2 Cells / metabolism
Substances
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Cytokines
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IL25 protein, human
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IL33 protein, human
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Interleukin-17
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Interleukin-33
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Interleukins
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NK Cell Lectin-Like Receptor Subfamily B
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Receptors, Immunologic
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Receptors, Prostaglandin
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prostaglandin D2 receptor