title: Staphylococcal exotoxins are strong inducers of IL-22: A potential role in atopic dermatitis.
abstract: BACKGROUND
  Patients with atopic dermatitis (AD) and psoriasis are frequently colonized with Staphylococcus aureus that produces staphylococcal enterotoxin B (SEB) and α-toxin. In patients with AD, S aureus colonization is positively correlated with the severity of their eczema. Moreover, IL-22-producing cells have been shown to accumulate in AD skin and to correlate with disease severity.
  
  
  OBJECTIVE
  To assess IL-22 production in response to SEB and sublytic α-toxin stimulation in patients with AD and psoriasis compared with healthy controls.
  
  
  METHODS
  IL-22 induction was investigated in PBMCs, T cells, and autologous cocultures of keratinocytes and T cells on SEB and α-toxin stimulation in a time-dependent and dose-dependent manner at the mRNA and protein (ELISA and flow cytometry) level. Anti-IL-1 receptor or anti-IL-6 antibodies were used in blocking experiments.
  
  
  RESULTS
  Staphylococcal enterotoxin B and sublytic α-toxin concentrations induced IL-22 production in PBMCs and isolated CD4(+) T cells. IL-22 secretion was enhanced by α-toxin stimulation in autologous cocultures of keratinocytes and T cells. In T cells and PBMCs from patients with AD, IL-22 secretion was significantly enhanced on α-toxin stimulation compared with patients with psoriasis and healthy controls.
  
  
  CONCLUSIONS
  Increased IL-22 secretion induced by staphylococcal exotoxins in the skin partially explains how skin colonization and infection with S aureus can contribute to chronic skin inflammation in AD.
authors.affiliation: Department of Dermatology and Allergy, Division of Immunodermatology and Allergy Research, Hannover Medical School, Hannover, Germany. niebuhr.margarete@mh-hannover.de
authors.forename: Margarete
authors.initials: M
authors.lastname: Niebuhr
authors.forename: Helena
authors.initials: H
authors.lastname: Scharonow
authors.forename: Merle
authors.initials: M
authors.lastname: Gathmann
authors.forename: Diana
authors.initials: D
authors.lastname: Mamerow
authors.forename: Thomas
authors.initials: T
authors.lastname: Werfel
mesh_terms: D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001427:Bacterial Toxins / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D018920:Coculture Techniques; D003876:Dermatitis, Atopic / Q000276:immunology* / Q000382:microbiology; D004768:Enterotoxins / Q000276:immunology / Q000378:metabolism; D006460:Hemolysin Proteins / Q000276:immunology / Q000378:metabolism; D006801:Humans; D015850:Interleukin-6 / Q000276:immunology; D007378:Interleukins / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D015603:Keratinocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D011565:Psoriasis / Q000276:immunology* / Q000382:microbiology; D017472:Receptors, Interleukin-1 / Q000276:immunology; D012867:Skin / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D000097043:Interleukin-22
chemical_list: D000911:Antibodies, Monoclonal; D001427:Bacterial Toxins; D004768:Enterotoxins; D006460:Hemolysin Proteins; D015850:Interleukin-6; D007378:Interleukins; D017472:Receptors, Interleukin-1; D000097043:Interleukin-22; C021091:staphylococcal alpha-toxin; C031818:enterotoxin B, staphylococcal