title: T cell-regulated neutrophilic inflammation in autoinflammatory diseases.
abstract: Previous studies of acute generalized exanthematous pustulosis, a peculiar drug hypersensitivity reaction, suggested that CXCL8-producing T cells regulate sterile, polymorphonuclear neutrophil-rich skin inflammations. In this study, we test the hypothesis of whether CXCL8-producing T cells are present in autoinflammatory diseases like pustular psoriasis and Behçet's disease. Immunohistochemistry of normal skin revealed few CD4+ and CD8+ T cells, few CXCL8+ cells, and no neutrophilic infiltration, whereas in acute exacerbations of atopic dermatitis, numerous CD4+ T cells but few CD8+ T cells, neutrophils, or CXCL8+ cells were detected. In contrast, a pronounced infiltration of neutrophils and of predominantly CD4+ T cells was observed in skin biopsies from pustular psoriasis, Behçet's disease, and acute generalized exanthematous pustulosis, with infiltrating T cells strongly positive for CXCL8 and the chemokine receptor CCR6. Skin-derived T cell clones from pustular skin reactions were positive for CCR6 but negative for CCR8 and secreted high amounts of CXCL8 and GM-CSF, often together with IFN-gamma and TNF-alpha after in vitro stimulation. Moreover, some skin-derived T cell clones from Behçet's disease and from pustular psoriasis predominantly produced CXCL8 and GM-CSF, but failed to secrete IL-5 and IFN-gamma. These cells might represent a particular subset as they differ from both Th1 as well as Th2 T cells and are associated with a unique, neutrophil-rich sterile inflammation. Our findings suggest that CXCL8/GM-CSF-producing T cells may orchestrate neutrophil-rich pathologies of chronic autoinflammatory diseases like pustular psoriasis and Behçet's disease.
authors.affiliation: Division of Allergology, Clinic of Rheumatology and Clinical Immunology/Allergology, Inselspital, University of Bern, Bern, Switzerland.
authors.forename: Monika
authors.initials: M
authors.lastname: Keller
authors.forename: Zoi
authors.initials: Z
authors.lastname: Spanou
authors.forename: Patrick
authors.initials: P
authors.lastname: Schaerli
authors.forename: Markus
authors.initials: M
authors.lastname: Britschgi
authors.forename: Nikhil
authors.initials: N
authors.lastname: Yawalkar
authors.forename: Michael
authors.initials: M
authors.lastname: Seitz
authors.forename: Peter M
authors.initials: PM
authors.lastname: Villiger
authors.forename: Werner J
authors.initials: WJ
authors.lastname: Pichler
mesh_terms: D000328:Adult; D000368:Aged; D001528:Behcet Syndrome / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D015704:CD4 Antigens / Q000276:immunology / Q000378:metabolism; D016827:CD8 Antigens / Q000276:immunology / Q000378:metabolism; D054418:Chemokine CCL20; D019742:Chemokines, CC / Q000096:biosynthesis / Q000276:immunology; D003876:Dermatitis, Atopic / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D005260:Female; D005434:Flow Cytometry; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis / Q000276:immunology; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation / Q000276:immunology*; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D016209:Interleukin-8 / Q000096:biosynthesis / Q000276:immunology; D019402:Macrophage Inflammatory Proteins / Q000096:biosynthesis / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000276:immunology*; D011565:Psoriasis / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D054399:Receptors, CCR6; D019707:Receptors, Chemokine / Q000096:biosynthesis / Q000276:immunology; D012867:Skin / Q000276:immunology / Q000378:metabolism; D012871:Skin Diseases / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000276:immunology
chemical_list: C108355:CCL20 protein, human; C106311:CCR6 protein, human; D015704:CD4 Antigens; D016827:CD8 Antigens; D054418:Chemokine CCL20; D019742:Chemokines, CC; D016209:Interleukin-8; D019402:Macrophage Inflammatory Proteins; D054399:Receptors, CCR6; D019707:Receptors, Chemokine; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor