Document Detail


Mechanical injury polarizes skin dendritic cells to elicit a T(H)2 response by inducing cutaneous thymic stromal lymphopoietin expression.
MedLine Citation:
PMID:  21050944     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Atopic dermatitis is characterized by scratching and by T(H)2-dominated immune response to cutaneously introduced antigens. Antigen application to skin mechanically injured by tape stripping results in T(H)2-dominated skin inflammation.
OBJECTIVE: To examine the effect of tape stripping on the capacity of skin dendritic cells (DCs) to polarize T cells toward a T(H)2 phenotype.
METHODS: CD11c(+) DCs were isolated from skin of BALB/c or C57BL/6 mice. Fluorescein isothiocyanate (FITC)(+) and FITC(-) DCs were isolated from draining lymph nodes (DLNs) 24 hours after painting the skin with FITC. DCs were assessed for their ability to induce cytokine secretion by ovalbumin-stimulated naive CD4(+) T cells from T cell receptor-ovalbumin transgenic DO11.10 mice. Cytokine mRNA levels were examined by quantitative PCR.
RESULTS: Dendritic cells isolated from the skin of wild-type, but not thymic stromal lymphopoietin (TSLP) receptor(-/-) or IL-10(-/-), mice 6 hours after tape stripping elicited significantly more IL-4 and IL-13 and significantly less IFN-γ production by CD4(+) cells than DCs isolated from unmanipulated skin, and expressed significantly more mRNA for the T(H)2 skewing molecules IL-10, Jagged1, and Jagged2, but significantly less mRNA for the T(H)1 skewing cytokine IL-12. CD11c(+)FITC(+) cells isolated from DLNs of shaved and tape stripped skin of wild-type, but not TSLP receptor(-/-) or IL-10(-/-), mice polarized T cells significantly more toward T(H)2 and expressed significantly more IL-10, Jagged1, and Jagged2 mRNA than CD11c(+)FITC(+) cells isolated from DLNs of shaved skin. Tape stripping significantly increased TSLP levels in the skin, and TSLP was shown to play an essential role in the T(H)2 polarization of skin DCs by tape stripping.
CONCLUSIONS: Tape stripping upregulates TSLP levels in the skin, which polarizes skin DCs to elicit a T(H)2 response via the induction of IL-10.
Authors:
Michiko K Oyoshi; Ryan P Larson; Steven F Ziegler; Raif S Geha
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Journal of allergy and clinical immunology     Volume:  126     ISSN:  1097-6825     ISO Abbreviation:  J. Allergy Clin. Immunol.     Publication Date:  2010 Nov 
Date Detail:
Created Date:  2010-11-05     Completed Date:  2010-12-10     Revised Date:  2011-09-26    
Medline Journal Info:
Nlm Unique ID:  1275002     Medline TA:  J Allergy Clin Immunol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  976-84, 984.e1-5     Citation Subset:  AIM; IM    
Copyright Information:
Copyright © 2010 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.
Affiliation:
Division of Immunology, Children's Hospital and Department of Pediatrics, Harvard Medical School, Boston, Mass 02115, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cytokines / biosynthesis*,  immunology
Dermatitis, Atopic / immunology,  metabolism
Langerhans Cells / immunology*,  metabolism
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Mice, Transgenic
Phenotype
Reverse Transcriptase Polymerase Chain Reaction
Skin / immunology*,  injuries,  metabolism
Th2 Cells / immunology*,  metabolism
Grant Support
ID/Acronym/Agency:
AI068731/AI/NIAID NIH HHS; AR-047417/AR/NIAMS NIH HHS; AR055695/AR/NIAMS NIH HHS; AR056113/AR/NIAMS NIH HHS; CA009537/CA/NCI NIH HHS; N01-AI-40030/AI/NIAID NIH HHS; R01 AI068731-04/AI/NIAID NIH HHS; R01 AR047417-01/AR/NIAMS NIH HHS; R01 AR055695-02/AR/NIAMS NIH HHS; R01 AR055695-03/AR/NIAMS NIH HHS; R01 AR056113-03/AR/NIAMS NIH HHS; R01 AR056113-04/AR/NIAMS NIH HHS; T32-GM007270/GM/NIGMS NIH HHS; //Howard Hughes Medical Institute
Chemical
Reg. No./Substance:
0/Cytokines; 0/thymic stromal lymphopoietin
Comments/Corrections

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