Dibutyl phthalate-induced thymic stromal lymphopoietin is required for Th2 contact hypersensitivity responses

J Immunol. 2010 Mar 15;184(6):2974-84. doi: 10.4049/jimmunol.0803478. Epub 2010 Feb 19.

Abstract

Thymic stromal lymphopoietin (TSLP) is an IL-7-related cytokine, produced by epithelial cells, that has been linked to atopic dermatitis and asthma; however, it remains unclear how TSLP shapes the adaptive immune response that causes these allergic disorders. In this study, we demonstrate a role for TSLP in a Th2 model of contact hypersensitivity in mice. TSLP is required for the development of Th2-type contact hypersensitivity induced by the hapten FITC in combination with the sensitizing agent dibutyl phthalate. TSLPR-deficient mice exhibited a dramatically reduced response, including markedly reduced local infiltration by eosinophils, Th2 cytokine production, and serum IgE levels, following FITC sensitization and challenge. The reduced response by TSLPR-deficient mice is likely due to decreased frequency and reduced T cell stimulatory function of skin-derived Ag-bearing FITC(+)CD11c(+) dendritic cells in draining lymph nodes following FITC sensitization. These data suggest that skin-derived dendritic cells are direct or indirect targets of TSLP in the development of type 2 immune responses in the skin, where TSLP drives their maturation, accumulation in skin draining lymph nodes, and ability to induce proliferation of naive allergen-specific T cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Allergens / administration & dosage
  • Allergens / immunology
  • Animals
  • Cell Differentiation / genetics
  • Cell Differentiation / immunology
  • Cell Line
  • Cell Migration Inhibition / genetics
  • Cell Migration Inhibition / immunology
  • Cell Proliferation
  • Cytokines / biosynthesis*
  • Cytokines / metabolism
  • Cytokines / physiology*
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism
  • Dendritic Cells / pathology
  • Dermatitis, Contact / genetics
  • Dermatitis, Contact / immunology*
  • Dermatitis, Contact / pathology
  • Dibutyl Phthalate / administration & dosage*
  • Dibutyl Phthalate / immunology
  • Disease Models, Animal
  • Epitopes, T-Lymphocyte / immunology
  • Immunoglobulins
  • Lymph Nodes / immunology
  • Lymph Nodes / metabolism
  • Lymph Nodes / pathology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Knockout
  • Plasticizers / administration & dosage
  • Receptors, Cytokine / deficiency
  • Receptors, Cytokine / metabolism
  • Receptors, Cytokine / physiology
  • Resting Phase, Cell Cycle / genetics
  • Resting Phase, Cell Cycle / immunology
  • Stromal Cells / immunology
  • Stromal Cells / metabolism
  • T-Lymphocytes / immunology
  • T-Lymphocytes / pathology
  • Th2 Cells / immunology*
  • Th2 Cells / metabolism
  • Thymic Stromal Lymphopoietin
  • Thymus Gland / cytology
  • Thymus Gland / immunology*
  • Thymus Gland / metabolism

Substances

  • Allergens
  • Cytokines
  • Epitopes, T-Lymphocyte
  • Immunoglobulins
  • Plasticizers
  • Receptors, Cytokine
  • Tslpr protein, mouse
  • Dibutyl Phthalate
  • Thymic Stromal Lymphopoietin
  • TSLP protein, mouse