MGL2+ Dermal Dendritic Cells Are Sufficient to Initiate Contact Hypersensitivity In Vivo
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Authors: | Yosuke Kumamoto Kaori Denda-Nagai Satoshi Aida Nobuaki Higashi Tatsuro Irimura |
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Institution: | Laboratory of Cancer Biology and Molecular Immunology, Graduate School of Pharmaceutical Sciences, the University of Tokyo, Tokyo, Japan.;New York University School of Medicine, United States of America |
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Abstract: | BackgroundDendritic cells (DCs) are the most potent antigen-presenting cells in the mammalian immune system. In the skin, epidermal Langerhans cells (LCs) and dermal dendritic cells (DDCs) survey for invasive pathogens and present antigens to T cells after migration to the cutaneous lymph nodes (LNs). So far, functional and phenotypic differences between these two DC subsets remain unclear due to lack of markers to identify DDCs.Methodology/Principal FindingsIn the present report, we demonstrated that macrophage galactose-type C-type lectin (MGL) 2 was exclusively expressed in the DDC subset in the skin-to-LN immune system. In the skin, MGL2 was expressed on the majority (about 88%) of MHCII+CD11c+ cells in the dermis. In the cutaneous LN, MGL2 expression was restricted to B220−CD8αloCD11b+CD11c+MHCIIhi tissue-derived DC. MGL2+DDC migrated from the dermis into the draining LNs within 24 h after skin sensitization with FITC. Distinct from LCs, MGL2+DDCs localized near the high endothelial venules in the outer T cell cortex. In FITC-induced contact hypersensitivity (CHS), adoptive transfer of FITC+MGL2+DDCs, but not FITC+MGL2−DCs into naive mice resulted in the induction of FITC-specific ear swelling, indicating that DDCs played a key role in initiation of immune responses in the skin.Conclusions/SignificanceThese results demonstrated the availability of MGL2 as a novel marker for DDCs and suggested the contribution of MGL2+ DDCs for initiating CHS. |
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