title: Characterization of innate lymphoid cells in human skin and blood demonstrates increase of NKp44+ ILC3 in psoriasis.
abstract: Innate lymphoid cells (ILCs) are increasingly appreciated as key regulators of tissue immunity. However, their role in human tissue homeostasis and disease remains to be fully elucidated. Here we characterize the ILCs in human skin from healthy individuals and from the inflammatory skin disease psoriasis. We show that a substantial proportion of IL-17A and IL-22 producing cells in the skin and blood of normal individuals and psoriasis patients are CD3-negative innate lymphocytes. Deep immunophenotyping of human ILC subsets showed a statistically significant increase in the frequency of circulating NKp44+ ILC3 in the blood of psoriasis patients compared with healthy individuals or atopic dermatitis patients. More than 50% of circulating NKp44+ ILC3 expressed cutaneous lymphocyte-associated antigen, indicating their potential for skin homing. Analysis of skin tissue revealed a significantly increased frequency of total ILCs in the skin compared with blood. Moreover, the frequency of NKp44+ ILC3 was significantly increased in non-lesional psoriatic skin compared with normal skin. A detailed time course of a psoriasis patient treated with anti-tumor necrosis factor showed a close association between therapeutic response, decrease in inflammatory skin lesions, and decrease of circulating NKp44+ ILC3. Overall, data from this initial observational study suggest a potential role for NKp44+ ILC3 in psoriasis pathogenesis.
authors.affiliation: St. John's Institute of Dermatology, King's College London, London, UK.|NIHR GSTT/KCL Comprehensive Biomedical Research Centre, Guy's & St. Thomas' NHS Foundation Trust, London, UK.
authors.forename: Federica
authors.initials: F
authors.lastname: Villanova
authors.affiliation: St. John's Institute of Dermatology, King's College London, London, UK.
authors.forename: Barry
authors.initials: B
authors.lastname: Flutter
authors.affiliation: St. John's Institute of Dermatology, King's College London, London, UK.|NIHR GSTT/KCL Comprehensive Biomedical Research Centre, Guy's & St. Thomas' NHS Foundation Trust, London, UK.
authors.forename: Isabella
authors.initials: I
authors.lastname: Tosi
authors.affiliation: St. John's Institute of Dermatology, King's College London, London, UK.|NIHR GSTT/KCL Comprehensive Biomedical Research Centre, Guy's & St. Thomas' NHS Foundation Trust, London, UK.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Grys
authors.affiliation: St. John's Institute of Dermatology, King's College London, London, UK.|NIHR GSTT/KCL Comprehensive Biomedical Research Centre, Guy's & St. Thomas' NHS Foundation Trust, London, UK.
authors.forename: Hemawtee
authors.initials: H
authors.lastname: Sreeneebus
authors.affiliation: St. John's Institute of Dermatology, King's College London, London, UK.|Dermatology Department, Middlesex University Hospital, UK.
authors.forename: Gayathri K
authors.initials: GK
authors.lastname: Perera
authors.affiliation: Dermatology Department, Queen Elizabeth Hospital, London UK.
authors.forename: Anna
authors.initials: A
authors.lastname: Chapman
authors.affiliation: St. John's Institute of Dermatology, King's College London, London, UK.
authors.forename: Catherine H
authors.initials: CH
authors.lastname: Smith
authors.affiliation: St. John's Institute of Dermatology, King's College London, London, UK.
authors.forename: Paola
authors.initials: P
authors.lastname: Di Meglio
authors.affiliation: St. John's Institute of Dermatology, King's College London, London, UK.|NIHR GSTT/KCL Comprehensive Biomedical Research Centre, Guy's & St. Thomas' NHS Foundation Trust, London, UK.
authors.forename: Frank O
authors.initials: FO
authors.lastname: Nestle
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D017252:CD3 Complex / Q000378:metabolism; D003876:Dermatitis, Atopic / Q000097:blood / Q000276:immunology* / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D006706:Homeostasis; D006801:Humans; D007113:Immunity, Innate; D016130:Immunophenotyping; D020381:Interleukin-17 / Q000276:immunology; D007378:Interleukins / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000166:cytology; D008214:Lymphocytes / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D055629:Natural Cytotoxicity Triggering Receptor 2 / Q000378:metabolism*; D011565:Psoriasis / Q000097:blood / Q000276:immunology* / Q000378:metabolism; D012867:Skin / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D000097043:Interleukin-22
chemical_list: D015415:Biomarkers; D017252:CD3 Complex; D020381:Interleukin-17; D007378:Interleukins; D055629:Natural Cytotoxicity Triggering Receptor 2; D000097043:Interleukin-22; C112837:NCR2 protein, human