Hapten sensitization to vaginal mucosa induces less recruitment of dendritic cells accompanying TGF-beta-expressing CD206(+) cells compared with skin

Introduction: Contact hypersensitivity (CHS), a type of delayed-type hypersensitivity, is induced by hapten exposure to the skin and mucosa. We previously reported that, in a murine model of CHS, the vaginal mucosa (VM) sensitization showed lower T-cell responses as compared with the abdominal skin sensitization. To investigate mechanisms of impaired CHS by the VM sensitization, we compared migration of hapten-captured dendritic cells (DCs) in the draining lymph nodes (dLNs) and recruitment of DCs at the sensitized local sites. Methods: Fluorescein isothiocyanate (FITC) or 2,4-dinitrofluorobenzene (DNFB) was used as hapten, and migration of FITC+ DCs in the dLNs and local recruitment of MHC class II+ and CD11c(+) cells were compared between abdominal skin and VM sensitization by flow cytometric analyses and immunohistochemistry. Expression of tumor growth factor (TGF)-beta at mRNA and protein levels, and local recruitment of CD206(+) cells were examined after VM sensitization. Results: VM sensitization showed less numbers of FITC+MHC class II-(high)CD11c(+) migratory DCs in the dLNs at 6 and 24 h, as compared with skin sensitization. Both skin and VM sensitization induced the recruitment of dermal/submucosal DCs at 6 h, but the number of submucosal DCs in the VM was significantly decreased at 24 h. VM showed persistently higher mRNA levels of TGF-beta 2/beta 3 expression than those of the skin before and after sensitization. In the VM sensitization, increment of CD206(+) MHC class II+ cells was observed especially at the deep lamina propria at 24 h. Most of CD206(+) cells were also positive for the binding to Fc chimeric TGF-beta receptor that interacts with all TGF-beta isoforms, suggesting TGF-beta expression. Conclusion: DC migration to dLNs and localization of DCs at the sensitized sites are limited in the VM sensitization. Our results suggest that the existence of TGF-beta-expressing CD206(+) cells may contribute less sensitization ability and CHS responses in the VM.