T cell-regulated neutrophilic inflammation in autoinflammatory diseases

J Immunol. 2005 Dec 1;175(11):7678-86. doi: 10.4049/jimmunol.175.11.7678.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Behcet Syndrome / immunology
  • Behcet Syndrome / metabolism
  • Behcet Syndrome / pathology
  • CD4 Antigens / immunology
  • CD4 Antigens / metabolism
  • CD8 Antigens / immunology
  • CD8 Antigens / metabolism
  • Chemokine CCL20
  • Chemokines, CC / biosynthesis
  • Chemokines, CC / immunology
  • Dermatitis, Atopic / immunology
  • Dermatitis, Atopic / metabolism
  • Dermatitis, Atopic / pathology
  • Female
  • Flow Cytometry
  • Granulocyte-Macrophage Colony-Stimulating Factor / biosynthesis
  • Granulocyte-Macrophage Colony-Stimulating Factor / immunology
  • Humans
  • Immunohistochemistry
  • Inflammation / immunology*
  • Interferon-gamma / biosynthesis
  • Interferon-gamma / immunology
  • Interleukin-8 / biosynthesis
  • Interleukin-8 / immunology
  • Macrophage Inflammatory Proteins / biosynthesis
  • Macrophage Inflammatory Proteins / immunology
  • Male
  • Middle Aged
  • Neutrophils / immunology*
  • Psoriasis / immunology
  • Psoriasis / metabolism
  • Psoriasis / pathology
  • Receptors, CCR6
  • Receptors, Chemokine / biosynthesis
  • Receptors, Chemokine / immunology
  • Skin / immunology
  • Skin / metabolism
  • Skin Diseases / immunology*
  • Skin Diseases / metabolism
  • Skin Diseases / pathology
  • T-Lymphocytes / immunology*
  • Tumor Necrosis Factor-alpha / biosynthesis
  • Tumor Necrosis Factor-alpha / immunology

Substances

  • CCL20 protein, human
  • CCR6 protein, human
  • CD4 Antigens
  • CD8 Antigens
  • Chemokine CCL20
  • Chemokines, CC
  • Interleukin-8
  • Macrophage Inflammatory Proteins
  • Receptors, CCR6
  • Receptors, Chemokine
  • Tumor Necrosis Factor-alpha
  • Interferon-gamma
  • Granulocyte-Macrophage Colony-Stimulating Factor