title: Composition of innate lymphoid cell subsets in the human skin: enrichment of NCR(+) ILC3 in lesional skin and blood of psoriasis patients.
abstract: Innate lymphoid cells (ILCs) are increasingly appreciated as important regulators of tissue homeostasis and inflammation. However, their role in human skin remains obscure. We found that healthy peripheral blood CD117(+) ILC3, lacking the natural cytotoxicity receptor (NCR) NKp44 (NCR(-) ILC3), CD117(-)NCR(-)CRTH2(-)CD161(+) ILC1, and CRTH2(+) ILC2, express the skin-homing receptor cutaneous lymphocyte antigen (CLA). NCR(+) ILC3 were scarce in peripheral blood. Consistently, we identified in normal skin ILC2 and NCR(-) ILC3, a small proportion of CD161(+) ILC1, and hardly any NCR(+) ILC3, whereas NCR(+) ILC3 were present in cultured dermal explants. The skin ILC2 and NCR(+) ILC3 subsets produced IL-13 and IL-22, respectively, upon cytokine stimulation. Remarkably, dermal NCR(-) ILC3 converted to NCR(+) ILC3 upon culture in IL-1β plus IL-23, cytokines known to be involved in psoriatic inflammation. In line with this observation, significantly increased proportions of NCR(+) ILC3 were present in lesional skin and peripheral blood of psoriasis patients as compared with skin and blood of healthy individuals, respectively, whereas the proportions of ILC2 and CD161(+) ILC1 remained unchanged. NCR(+) ILC3 from skin and blood of psoriasis patients produced IL-22, which is regarded as a key driver of epidermal thickening, suggesting that NCR(+) ILC3 may participate in psoriasis pathology.
authors.affiliation: Department of Dermatology, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Marcel B M
authors.initials: MBM
authors.lastname: Teunissen
authors.affiliation: Department of Hematology, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: J Marius
authors.initials: JM
authors.lastname: Munneke
authors.affiliation: Tytgat Institute for Liver and Intestinal Research, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Jochem H
authors.initials: JH
authors.lastname: Bernink
authors.affiliation: Department of Dermatology, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Phyllis I
authors.initials: PI
authors.lastname: Spuls
authors.affiliation: Department of Dermatology, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Pieter C M
authors.initials: PCM
authors.lastname: Res
authors.affiliation: Tytgat Institute for Liver and Intestinal Research, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Anje
authors.initials: A
authors.lastname: Te Velde
authors.affiliation: Dermatology and Venereology Unit, Department of Medicine Solna, Karolinska Institutet, Solna, Sweden.
authors.forename: Stanley
authors.initials: S
authors.lastname: Cheuk
authors.affiliation: Department of Dermatology, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Marijke W D
authors.initials: MWD
authors.lastname: Brouwer
authors.affiliation: Department of Dermatology, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Stef P
authors.initials: SP
authors.lastname: Menting
authors.affiliation: Dermatology and Venereology Unit, Department of Medicine Solna, Karolinska Institutet, Solna, Sweden.
authors.forename: Liv
authors.initials: L
authors.lastname: Eidsmo
authors.affiliation: Department of Cell Biology and Histology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. Electronic address: hergen.spits@amc.uva.nl.
authors.forename: Hergen
authors.initials: H
authors.lastname: Spits
authors.affiliation: Department of Hematology, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Mette D
authors.initials: MD
authors.lastname: Hazenberg
authors.affiliation: Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Huddinge, Sweden.
authors.forename: Jenny
authors.initials: J
authors.lastname: Mjösberg
mesh_terms: D000328:Adult; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology / Q000378:metabolism; D001402:B-Lymphocytes / Q000166:cytology / Q000378:metabolism; D002461:Cell Line, Transformed; D019070:Cell Lineage / Q000276:immunology; D020405:Dermis / Q000166:cytology / Q000276:immunology*; D000078404:Epidermal Cells; D004817:Epidermis / Q000276:immunology*; D006801:Humans; D016130:Immunophenotyping; D053583:Interleukin-1beta / Q000276:immunology / Q000378:metabolism; D053759:Interleukin-23 / Q000276:immunology / Q000378:metabolism; D007378:Interleukins / Q000276:immunology / Q000378:metabolism; D008214:Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000276:immunology / Q000378:metabolism; D055629:Natural Cytotoxicity Triggering Receptor 2 / Q000276:immunology* / Q000378:metabolism; D019009:Proto-Oncogene Proteins c-kit / Q000276:immunology / Q000378:metabolism; D011565:Psoriasis / Q000097:blood / Q000276:immunology* / Q000473:pathology; D011971:Receptors, Immunologic / Q000276:immunology / Q000378:metabolism; D011982:Receptors, Prostaglandin / Q000276:immunology / Q000378:metabolism; D000097043:Interleukin-22
chemical_list: D000945:Antigens, Differentiation, T-Lymphocyte; D053583:Interleukin-1beta; D053759:Interleukin-23; D007378:Interleukins; D008562:Membrane Glycoproteins; D055629:Natural Cytotoxicity Triggering Receptor 2; D019009:Proto-Oncogene Proteins c-kit; D011971:Receptors, Immunologic; D011982:Receptors, Prostaglandin; D000097043:Interleukin-22; C063419:CTAGE1 protein, human; C112837:NCR2 protein, human; C036293:prostaglandin D2 receptor