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

RP Larson, SC Zimmerli, MR Comeau… - The Journal of …, 2010 - journals.aai.org
RP Larson, SC Zimmerli, MR Comeau, A Itano, M Omori, M Iseki, C Hauser, SF Ziegler
The Journal of Immunology, 2010journals.aai.org
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 …
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.
journals.aai.org