title: CD326(lo)CD103(lo)CD11b(lo) dermal dendritic cells are activated by thymic stromal lymphopoietin during contact sensitization in mice.
abstract: The cytokine thymic stromal lymphopoietin (TSLP) is produced by epithelia exposed to the contact sensitizer dibutyl phthalate (DBP), and it is critical for the induction of Th2 immune responses by DBP-FITC. TSLP is thought to act on dendritic cells (DC), but the precise DC subsets involved in the response to TSLP remain to be fully characterized. In this study we show that a subset of CD326(lo)CD103(lo)CD11b(lo) dermal DC, which we termed "triple-negative (TN) DC," is highly responsive to TSLP. In DBP-FITC-treated mice, TN DC upregulated expression of CD86 and rapidly migrated to the draining lymph node to become the most abundant skin-derived DC subset at 24 and 48 h after sensitization. None of these responses was observed in TSLPR-deficient mice. In contrast, TN DC numbers were not increased after treatment with the allergen house dust mite or the bacteria Escherichia coli and bacillus Calmette-Guérin, which increased other DC subsets. In vivo, treatment with rTSLP preferentially increased the numbers of TN DC in lymph nodes. In vitro, TN DC responded to rTSLP treatment with a higher level of STAT5 phosphorylation compared with other skin-derived DC subsets. The TN DC subset shared the morphology, phenotype, and developmental requirements of conventional DC, depending on FLT3 expression for their optimal development from bone marrow precursors, and CCR7 for migration to the draining lymph node. Thus, TN DC represent a dermal DC subset that should be considered in future studies of TSLP-dependent contact sensitization and skin immune responses.
authors: Malaghan Institute of Medical Research, Wellington 6012, New Zealand; University of Otago, Wellington 6021, New Zealand;
authors: Sotaro
authors: S
authors: Ochiai
authors: Centenary Institute, Sydney, New South Wales 2042, Australia;
authors: Ben
authors: B
authors: Roediger
authors: Centenary Institute, Sydney, New South Wales 2042, Australia;
authors: Arby
authors: A
authors: Abtin
authors: Centenary Institute, Sydney, New South Wales 2042, Australia;
authors: Elena
authors: E
authors: Shklovskaya
authors: Centenary Institute, Sydney, New South Wales 2042, Australia;
authors: Barbara
authors: B
authors: Fazekas de St Groth
authors: Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892; and.
authors: Hidehiro
authors: H
authors: Yamane
authors: Centenary Institute, Sydney, New South Wales 2042, Australia; Sydney Medical School, Sydney, New South Wales 2006, Australia.
authors: Wolfgang
authors: W
authors: Weninger
authors: Malaghan Institute of Medical Research, Wellington 6012, New Zealand;
authors: Graham
authors: G
authors: Le Gros
authors: Malaghan Institute of Medical Research, Wellington 6012, New Zealand; fronchese@malaghan.org.nz.
authors: Franca
authors: F
authors: Ronchese
mesh_terms: D000818:Animals; D015703:Antigens, CD; D039741:Antigens, Dermatophagoides / Q000276:immunology / Q000633:toxicity; D039481:CD11b Antigen; D018955:CD36 Antigens; D016207:Cytokines / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology* / Q000473:pathology; D017449:Dermatitis, Allergic Contact / Q000276:immunology* / Q000473:pathology; D020405:Dermis / Q000276:immunology* / Q000473:pathology; D004926:Escherichia coli / Q000276:immunology; D039001:Integrin alpha Chains; D008198:Lymph Nodes / Q000276:immunology / Q000473:pathology; D051379:Mice; D009163:Mycobacterium bovis / Q000276:immunology; D054400:Receptors, CCR7 / Q000276:immunology; D050799:STAT5 Transcription Factor / Q000276:immunology; D000094632:Thymic Stromal Lymphopoietin
chemical_list: D015703:Antigens, CD; D039741:Antigens, Dermatophagoides; D039481:CD11b Antigen; D018955:CD36 Antigens; C515371:Ccr7 protein, mouse; D016207:Cytokines; D039001:Integrin alpha Chains; D054400:Receptors, CCR7; D050799:STAT5 Transcription Factor; C091367:alpha E integrins; D000094632:Thymic Stromal Lymphopoietin