Human epithelial cells trigger dendritic cell mediated allergic inflammation by producing TSLP

Nat Immunol. 2002 Jul;3(7):673-80. doi: 10.1038/ni805. Epub 2002 Jun 10.

Abstract

Whether epithelial cells play a role in triggering the immune cascade leading to T helper 2 (T(H)2)-type allergic inflammation is not known. We show here that human thymic stromal lymphopoietin (TSLP) potently activated CD11c(+) dendritic cells (DCs) and induced production of the T(H)2-attracting chemokines TARC (thymus and activation-regulated chemokine; also known as CCL17) and MDC (macrophage-derived chemokine; CCL22). TSLP-activated DCs primed naïve T(H) cells to produce the proallergic cytokines interleukin 4 (IL-4), IL-5, IL-13 and tumor necrosis factor-alpha, while down-regulating IL-10 and interferon-gamma. TSLP was highly expressed by epithelial cells, especially keratinocytes from patients with atopic dermatitis. TSLP expression was associated with Langerhans cell migration and activation in situ. These findings shed new light on the function of human TSLP and the role played by epithelial cells and DCs in initiating allergic inflammation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Biomarkers
  • CD11 Antigens*
  • CD4-Positive T-Lymphocytes / cytology
  • CD4-Positive T-Lymphocytes / immunology
  • Cell Division
  • Cells, Cultured
  • Coculture Techniques
  • Cytokines / genetics
  • Cytokines / immunology*
  • Cytokines / pharmacology
  • Dendritic Cells / cytology
  • Dendritic Cells / drug effects
  • Dendritic Cells / immunology*
  • Dermatitis, Atopic / immunology*
  • Dermatitis, Atopic / pathology
  • Epithelial Cells / cytology
  • Epithelial Cells / immunology
  • Gene Expression
  • Humans
  • Interleukin-7 / immunology*
  • Interleukin-7 / pharmacology
  • Langerhans Cells / cytology
  • Langerhans Cells / immunology
  • Palatine Tonsil / immunology
  • RNA, Messenger
  • Skin / immunology
  • Skin / pathology
  • Th2 Cells / cytology
  • Th2 Cells / immunology*
  • Thymus Gland / immunology*

Substances

  • Biomarkers
  • CD11 Antigens
  • Cytokines
  • Interleukin-7
  • RNA, Messenger
  • thymic stromal lymphopoietin