期刊
JOURNAL OF IMMUNOLOGY
卷 184, 期 6, 页码 2974-2984出版社
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.0803478
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资金
- National Institutes of Health [AI44259, AI68731, AR56113, AR55695]
- Swiss National Foundation [310000-109716]
- Training Grant [CA009537, T32-GM007270]
- Howard Hughes Institute
- Grants-in-Aid for Scientific Research [21790488] Funding Source: KAKEN
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. The Journal of Immunology, 2010, 184: 2974-2984.
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