Hapten sensitization to vaginal mucosa induces less recruitment of dendritic cells accompanying TGF‐β‐expressing CD206⁺ cells compared with skin

Abstract

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)-β 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 IIhigh 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-β2/β3 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-β receptor that interacts with all TGF-β isoforms, suggesting TGF-β 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

CTLA-4 suppresses hapten-induced contact hypersensitivity in atopic dermatitis model mice

“…Migratory DCs were analyzed as previously described 34 . Flow cytometric experiments were conducted on draining LN cells collected from the axillary/inguinal LNs one day after sensitization.…”