Mechanical injury polarizes skin dendritic cells to elicit a TH2 response by inducing cutaneous thymic stromal lymphopoietin expression

Background Atopic dermatitis is characterized by scratching and by TH2-dominated immune response to cutaneously introduced antigens. Antigen application to skin mechanically injured by tape stripping results in TH2-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 TH2 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 TH2 skewing molecules IL-10, Jagged1, and Jagged2, but significantly less mRNA for the TH1 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 TH2 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 TH2 polarization of skin DCs by tape stripping. Conclusions Tape stripping upregulates TSLP levels in the skin, which polarizes skin DCs to elicit a TH2 response via the induction of IL-10.