Dibutyl phthalate-induced thymic stromal lymphopoietin is required for Th2 contact hypersensitivity responses.
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.
Larson
Ryan P
RP
Department of Immunology, University of Washington, Seattle, WA 98195, USA.
Zimmerli
Simone C
SC
Comeau
Michael R
MR
Itano
Andrea
A
Omori
Miyuki
M
Iseki
Masanori
M
Hauser
Conrad
C
Ziegler
Steven F
SF
D000485:Allergens / Q000008:administration & dosage / Q000276:immunology; D000818:Animals; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002460:Cell Line; D002464:Cell Migration Inhibition / Q000235:genetics / Q000276:immunology; D049109:Cell Proliferation; D016207:Cytokines / Q000096:biosynthesis* / Q000378:metabolism / Q000502:physiology*; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D003877:Dermatitis, Contact / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D003993:Dibutyl Phthalate / Q000008:administration & dosage* / Q000276:immunology; D004195:Disease Models, Animal; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D007136:Immunoglobulins; D008198:Lymph Nodes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D010968:Plasticizers / Q000008:administration & dosage; D018121:Receptors, Cytokine / Q000172:deficiency / Q000378:metabolism / Q000502:physiology; D016192:Resting Phase, Cell Cycle / Q000235:genetics / Q000276:immunology; D017154:Stromal Cells / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D000094632:Thymic Stromal Lymphopoietin
D000485:Allergens; D016207:Cytokines; D018984:Epitopes, T-Lymphocyte; D007136:Immunoglobulins; D010968:Plasticizers; D018121:Receptors, Cytokine; C410591:Tslpr protein, mouse; D003993:Dibutyl Phthalate; D000094632:Thymic Stromal Lymphopoietin; C000721967:TSLP protein, mouse