title: Group 2 Innate Lymphoid Cells Express Functional NKp30 Receptor Inducing Type 2 Cytokine Production.
abstract: Group 2 innate lymphoid cells (ILC2) are important in effector functions for eliciting allergic inflammation, parasite defense, epithelial repair, and lipid homeostasis. ILC2 lack rearranged Ag-specific receptors, and although many soluble factors such as cytokines and lipid mediators can influence ILC2, direct interaction of these cells with the microenvironment and other cells has been less explored. Natural cytotoxicity receptors are expressed by subsets of group 1 ILC and group 3 ILC and thought to be important for their effector function, but they have not been shown to be expressed by ILC2. Therefore, we sought to investigate the expression and functional properties of the natural cytotoxicity receptor NKp30 on human ILC2. A subset of ex vivo and cultured ILC2 express NKp30 that upon interaction with its cognate activatory ligand B7-H6 induces rapid production of type 2 cytokines. This interaction can be blocked by NKp30 blocking Ab and an inhibitory ligand, galectin-3. Higher expression of B7-H6 was observed in lesional skin biopsies of patients with atopic dermatitis, and incubation of keratinocytes with proinflammatory and type 2 cytokines upregulated B7-H6, leading to increased ILC2 cytokine production. NKp30-B7-H6 interaction is a novel cell contact mechanism that mediates activation of ILC2 and identifies a potential target for the development of novel therapeutics for atopic dermatitis and other atopic diseases.
authors.affiliation: Medical Research Council Human Immunology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford OX3 9DS, United Kingdom;
authors.forename: Maryam
authors.initials: M
authors.lastname: Salimi
authors.affiliation: Oxford National Institute for Health Research Biomedical Research Centre, Translational Immunology Laboratory, Nuffield Department of Medicine, John Radcliffe Hospital, University of Oxford, Oxford OX3 9DS, United Kingdom;
authors.forename: Luzheng
authors.initials: L
authors.lastname: Xue
authors.affiliation: Medical Research Council Laboratory of Molecular Biology, Cambridge CB2 0QH, United Kingdom;
authors.forename: Helen
authors.initials: H
authors.lastname: Jolin
authors.affiliation: Medical Research Council Laboratory of Molecular Biology, Cambridge CB2 0QH, United Kingdom;
authors.forename: Clare
authors.initials: C
authors.lastname: Hardman
authors.affiliation: Department of Infection, Immunity and Inflammation, National Institute for Health Research Leicester Respiratory Biomedical Research Unit, University of Leicester, Leicester LE3 9QP, United Kingdom; and Medical Research Council and Asthma UK Centre in Allergic Mechanisms of Asthma, King's College London, London WC2R 2LS, United Kingdom.
authors.forename: David J
authors.identifier: http://orcid.org/0000-0003-3821-9596
authors.initials: DJ
authors.lastname: Cousins
authors.affiliation: Medical Research Council Laboratory of Molecular Biology, Cambridge CB2 0QH, United Kingdom;
authors.forename: Andrew N J
authors.initials: AN
authors.lastname: McKenzie
authors.affiliation: Medical Research Council Human Immunology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford OX3 9DS, United Kingdom; graham.ogg@ndm.ox.ac.uk.
authors.forename: Graham S
authors.identifier: http://orcid.org/0000-0002-3097-045X
authors.initials: GS
authors.lastname: Ogg
mesh_terms: D019138:Antibodies, Blocking / Q000494:pharmacology; D060887:B7 Antigens / Q000378:metabolism*; D001798:Blood Proteins; D002460:Cell Line; D016207:Cytokines / Q000096:biosynthesis / Q000494:pharmacology; D003876:Dermatitis, Atopic / Q000276:immunology*; D004817:Epidermis / Q000378:metabolism; D037502:Galectin 3 / Q000494:pharmacology; D037161:Galectins; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology; D007249:Inflammation / Q000276:immunology; D015603:Keratinocytes / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology*; D008214:Lymphocytes / Q000276:immunology* / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D055628:Natural Cytotoxicity Triggering Receptor 3 / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000378:metabolism*
chemical_list: D019138:Antibodies, Blocking; D060887:B7 Antigens; D001798:Blood Proteins; D016207:Cytokines; D037502:Galectin 3; D037161:Galectins; C428445:LGALS3 protein, human; C542363:NCR3LG1 protein, human; D016328:NF-kappa B; D055628:Natural Cytotoxicity Triggering Receptor 3