Atopic dermatitis and skin diseaseLangerhans cells are critical in epicutaneous sensitization with protein antigen via thymic stromal lymphopoietin receptor signaling
Section snippets
Animals and bone marrow chimera
C57BL6 (B6) and BALB/c mice were purchased from Japan SLC (Shizuoka, Japan). OT-II T-cell receptor transgenic mice were purchased from the Jackson Laboratory (Bar Harbor, Me). Langerin-diphtheria toxin subunit A (DTA) mice were generated by Dr Daniel Kaplan,19 and Langerin-enhanced green fluorescent protein (eGFP)-diphtheria toxin receptor (DTR) knock-in mice were kindly provided by Dr Bernard Mallissen (CIML, Institut National de la Santé et de la Recherche Médicale, Marseille, France).
TSLPR−/−
LC depletion impaired the development of OVA-induced allergic skin dermatitis model
To assess the role of LCs in epicutaneous sensitization with protein antigens and induction of IgE, we applied OVA to mice epicutaneously.22 In this model, we observed a rise in OVA-specific serum IgE and IgG1 levels, both of which are induced in a TH2-dependent manner, as well as the development of dermatitis characterized by the infiltration of CD3+ T cells, eosinophils, and neutrophils and local expression of mRNA for the cytokines IL-4, IL-5, and IFN-γ.22 These findings exhibited
Discussion
In this study, we have demonstrated that LCs are the essential cutaneous DC subset in the induction of IgE upon epicutaneous sensitization with protein antigens. We also found that TSLPR expression on LCs is enhanced upon protein antigen exposure to the skin and that LCs plays an important role in this process through TSLP-TSLPR signaling. In addition, we have demonstrated that TSLP stimulation causes LCs to express OX40L as shown previously in human studies and that BM-derived DCs induce TH2
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This work was supported in part by Grants-in-Aid for Scientific Research from the Ministries of Education, Culture, Sports, Science and Technology (to K.K.) and by a Grant-in-Aid from the Japan Society for the Promotion of Science Fellows (to S.N.). This work was also supported by a grant from the NIH (AR056632 to D.H.K.) and the American Skin Association. B.Z.I. was supported by a grant from the Dermatology Foundation.
Disclosure of potential conflict of interest: The authors declare that they have no relevant conflicts of interest.