Staphylococcal exotoxins are strong inducers of IL-22: A potential role in atopic dermatitis

• Published in: Journal of allergy and clinical immunology 2010-12, Vol.126 (6), p.1176-1183.e4
• Main Authors: Niebuhr, Margarete, MD, Scharonow, Helena, MS, Gathmann, Merle, MS, Mamerow, Diana, MS, Werfel, Thomas, MD
• Format: Article
• Language: English
• Subjects: Allergic diseases; Allergy and Immunology; Antibodies, Monoclonal - pharmacology; atopic dermatitis; Bacterial diseases; Bacterial Toxins - immunology; Bacterial Toxins - metabolism; Biological and medical sciences; Cells, Cultured; Coculture Techniques; Dehydrogenases; Dermatitis; Dermatitis, Atopic - immunology; Dermatitis, Atopic - microbiology; Enterotoxins - immunology; Enterotoxins - metabolism; Epidermal growth factor; Experiments; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Hemolysin Proteins - immunology; Hemolysin Proteins - metabolism; human; Human bacterial diseases; Humans; IL-22; Immunopathology; Infectious diseases; Interleukin-22; Interleukin-6 - immunology; Interleukins - biosynthesis; Interleukins - genetics; Interleukins - immunology; Keratinocytes - immunology; Keratinocytes - metabolism; Keratinocytes - pathology; Lymphocytes; Medical sciences; Psoriasis; Psoriasis - immunology; Psoriasis - microbiology; Receptors, Interleukin-1 - immunology; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; SEB; Skin; Skin - pathology; Skin allergic diseases. Stinging insect allergies; Skin diseases; Staphylococcal infections, streptococcal infections, pneumococcal infections; Staphylococcus aureus; T-Lymphocytes - immunology; T-Lymphocytes - metabolism; T-Lymphocytes - pathology; TH22; α-toxin
• ISSN: 0091-6749; 1097-6825
• DOI: 10.1016/j.jaci.2010.07.041

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. Conclusion 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.