title: Streptococcus pyogenes-induced cutaneous lymphocyte antigen-positive T cell-dependent epidermal cell activation triggers TH17 responses in patients with guttate psoriasis.
abstract: Guttate psoriasis (GP) is characterized by acute onset of small, rounded psoriatic lesions. Although this particular phenotype of psoriasis is usually associated with streptococcal throat infections and mainly occurs in HLA-Cw6(+) patients, the specific immunologic response to this innate stimulus that causes these skin lesions is poorly understood.
  
  
  
  This study aims to elucidate how key cellular elements of patients with GP respond to Streptococcus pyogenes and whether this initial immune response is favored by the genetic and environmental background of these patients.
  
  
  
  Circulating memory T cells and autologous epidermal cells from samples from either patients with GP (n = 14) or healthy control subjects (n = 6) were cocultured ex vivo in the presence of an S pyogenes extract. Levels of the psoriasis-associated cytokines IL-17A, IL-17F, IFN-γ, TNF-α, IL-6, and IL-8 were determined. The expression of several genes with increased (DEFB4, S100A7, LCN2, IL36G, IL8, CXCL9, CXCL10, and CXCL11) or decreased (FLG and LOR) transcripts in psoriatic lesions was examined in keratinocytes treated with coculture supernatants.
  
  
  
  When skin-homing effector memory cutaneous lymphocyte antigen-positive T cells were used in cocultures, a TH17-dominant response was observed, as reflected by the higher amounts of IL-17A and IL-17F than IFN-γ. Moreover, a higher TH17 response was observed in cells isolated from patients with flares associated with a streptococcal tonsillitis and with the HLA-Cw6 allele (cohort 1). In addition, in normal keratinocytes the supernatants from these cocultures induced an increase in IL-17-associated genes, such as DEFB4, S100A7, LCN2, IL36G, and IL8 but a decrease in FLG and LOR, thereby confirming the role of activated TH17 cells.
  
  
  
  This study reveals a dominant TH17 response of cutaneous lymphocyte antigen-positive T cells activated by epidermal cells and S pyogenes in patients with GP.
authors.affiliation: Translational Immunology, Department of Cellular Biology, Physiology and Immunology, Universitat de Barcelona, Barcelona, Spain.
authors.forename: Ester
authors.initials: E
authors.lastname: Ruiz-Romeu
authors.affiliation: Department of Dermatology, Hospital del Mar, Research Group in Inflammatory Dermatologic Diseases, IMIM, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Ferran
authors.affiliation: Hospital Sant Jaume de Calella, Barcelona, Spain.
authors.forename: Marc
authors.initials: M
authors.lastname: Sagristà
authors.affiliation: Laboratori de Referència de Catalunya, El Prat de Llobregat, Barcelona, Spain.
authors.forename: Julià
authors.initials: J
authors.lastname: Gómez
authors.affiliation: Department of Dermatology, Hospital del Mar, Research Group in Inflammatory Dermatologic Diseases, IMIM, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Giménez-Arnau
authors.affiliation: Department of Dermatovenerology and Oncodermatolgy, Semmelweis Egyetem, Budapest, Hungary.
authors.forename: Krisztina
authors.initials: K
authors.lastname: Herszenyi
authors.affiliation: Department of Dermatovenerology and Oncodermatolgy, Semmelweis Egyetem, Budapest, Hungary.
authors.forename: Péter
authors.initials: P
authors.lastname: Hóllo
authors.affiliation: Macrophage Biology, Department of Cellular Biology, Physiology and Immunology, Universitat de Barcelona, Barcelona, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Celada
authors.affiliation: Department of Dermatology, Hospital del Mar, Research Group in Inflammatory Dermatologic Diseases, IMIM, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Ramon
authors.initials: R
authors.lastname: Pujol
authors.affiliation: Translational Immunology, Department of Cellular Biology, Physiology and Immunology, Universitat de Barcelona, Barcelona, Spain. Electronic address: luis.santamaria@ub.edu.
authors.forename: Luis F
authors.initials: LF
authors.lastname: Santamaria-Babí
mesh_terms: D000328:Adult; D000368:Aged; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism*; D016022:Case-Control Studies; D016207:Cytokines / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D000078404:Epidermal Cells; D004817:Epidermis / Q000276:immunology* / Q000378:metabolism; D005260:Female; D000091344:Filaggrin Proteins; D015870:Gene Expression; D006801:Humans; D007156:Immunologic Memory; D020381:Interleukin-17 / Q000096:biosynthesis; D007381:Intermediate Filament Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008875:Middle Aged; D011565:Psoriasis / Q000175:diagnosis / Q000209:etiology* / Q000378:metabolism*; D012720:Severity of Illness Index; D013297:Streptococcus pyogenes / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D058504:Th17 Cells / Q000276:immunology* / Q000378:metabolism*; D055815:Young Adult
chemical_list: D000945:Antigens, Differentiation, T-Lymphocyte; C063419:CTAGE1 protein, human; D016207:Cytokines; D004268:DNA-Binding Proteins; C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D020381:Interleukin-17; D007381:Intermediate Filament Proteins; C422449:LORARF protein, human; D008562:Membrane Glycoproteins
keywords: HLA-Cw*0602; T(H)17; cutaneous lymphocyte antigen; guttate psoriasis; streptococcal pharyngitis