title: Identification of a novel proinflammatory human skin-homing Vγ9Vδ2 T cell subset with a potential role in psoriasis.
abstract: γδ T cells mediate rapid tissue responses in murine skin and participate in cutaneous immune regulation including protection against cancer. The role of human γδ cells in cutaneous homeostasis and pathology is characterized poorly. In this study, we show in vivo evidence that human blood contains a distinct subset of proinflammatory cutaneous lymphocyte Ag and CCR6-positive Vγ9Vδ2 T cells, which is rapidly recruited into perturbed human skin. Vγ9Vδ2 T cells produced an array of proinflammatory mediators including IL-17A and activated keratinocytes in a TNF-α- and IFN-γ-dependent manner. Examination of the common inflammatory skin disease psoriasis revealed a striking reduction of circulating Vγ9Vδ2 T cells in psoriasis patients compared with healthy controls and atopic dermatitis patients. Decreased numbers of circulating Vγ9Vδ2 T cells normalized after successful treatment with psoriasis-targeted therapy. Taken together with the increased presence of Vγ9Vδ2 T cells in psoriatic skin, these data indicate redistribution of Vγ9Vδ2 T cells from the blood to the skin compartment in psoriasis. In summary, we report a novel human proinflammatory γδ T cell involved in skin immune surveillance with immediate response characteristics and with potential clinical relevance in inflammatory skin disease.
authors.affiliation: Cutaneous Medicine and Immunotherapy Unit, St. John's Institute of Dermatology, King's College London, London SE1 9RT, United Kingdom.
authors.forename: Ute
authors.initials: U
authors.lastname: Laggner
authors.forename: Paola
authors.initials: P
authors.lastname: Di Meglio
authors.forename: Gayathri K
authors.initials: GK
authors.lastname: Perera
authors.forename: Christian
authors.initials: C
authors.lastname: Hundhausen
authors.forename: Katie E
authors.initials: KE
authors.lastname: Lacy
authors.forename: Niwa
authors.initials: N
authors.lastname: Ali
authors.forename: Catherine H
authors.initials: CH
authors.lastname: Smith
authors.forename: Adrian C
authors.initials: AC
authors.lastname: Hayday
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Nickoloff
authors.forename: Frank O
authors.initials: FO
authors.lastname: Nestle
mesh_terms: D000328:Adult; D000945:Antigens, Differentiation, T-Lymphocyte / Q000096:biosynthesis / Q000276:immunology; D002469:Cell Separation; D018925:Chemokines / Q000032:analysis / Q000096:biosynthesis; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011565:Psoriasis / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology*; D054399:Receptors, CCR6 / Q000096:biosynthesis / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012867:Skin / Q000276:immunology* / Q000473:pathology*; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*
chemical_list: D000945:Antigens, Differentiation, T-Lymphocyte; C106311:CCR6 protein, human; D018925:Chemokines; D016692:Receptors, Antigen, T-Cell, gamma-delta; D054399:Receptors, CCR6