Mechanical injury polarizes skin dendritic cells to elicit a T(H)2 response by inducing cutaneous thymic stromal lymphopoietin expression.
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.
Division of Immunology, Children's Hospital and Department of Pediatrics, Harvard Medical School, Boston, Mass 02115, USA.
Michiko K
MK
Oyoshi
Ryan P
RP
Larson
Steven F
SF
Ziegler
Raif S
RS
Geha
D000818:Animals; D016207:Cytokines / Q000096:biosynthesis* / Q000276:immunology; D003876:Dermatitis, Atopic / Q000276:immunology / Q000378:metabolism; D007801:Langerhans Cells / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010641:Phenotype; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012867:Skin / Q000276:immunology* / Q000293:injuries / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism; D000094632:Thymic Stromal Lymphopoietin
D016207:Cytokines; D000094632:Thymic Stromal Lymphopoietin; C000721967:TSLP protein, mouse