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

• DOI: 10.1038/ni.2104
• Publication Date: 2011-09-11T13:20:50Z
• Authors: Jenny M Mjösberg; Sara Trifari; Natasha K Crellin; Charlotte P Peters; Cornelis M van Dr...; Berber Piet; Wytske J Fokkens; Tom Cupedo; Hergen Spits
• Keywords: Adult; Receptors, Prostaglandin; Immunophenotyping; 03 medical and health sciences; Nasal Polyps; 0302 clinical medicine; SDG 3 - Good Health and Well-being; Humans; Cell Lineage; Lymphocytes; Receptors, Immunologic; Sinusitis; Cells, Cultured; Rhinitis; Interleukins; Interleukin-17; Cell Differentiation; Interleukin-33; Immunity, Innate; 3. Good health; Intestines; EMC MM-02-41-04; Chronic Disease; Cytokines; NK Cell Lectin-Like Receptor Subfamily B

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.