MGL2 Dermal dendritic cells are sufficient to initiate contact hypersensitivity in vivo.
BACKGROUND
Dendritic 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.


RESULTS
In 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(-)CD8alpha(lo)CD11b(+)CD11c(+)MHCII(hi) 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
These results demonstrated the availability of MGL2 as a novel marker for DDCs and suggested the contribution of MGL2(+) DDCs for initiating CHS.
Laboratory of Cancer Biology and Molecular Immunology, Graduate School of Pharmaceutical Sciences, the University of Tokyo, Tokyo, Japan.
Yosuke
Y
Kumamoto
Kaori
K
Denda-Nagai
Satoshi
S
Aida
Nobuaki
N
Higashi
Tatsuro
T
Irimura
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D001212:Asialoglycoproteins / Q000378:metabolism; D039481:CD11b Antigen / Q000378:metabolism; D039521:CD11c Antigen / Q000378:metabolism; D016827:CD8 Antigens / Q000378:metabolism; D002465:Cell Movement / Q000502:physiology; D003877:Dermatitis, Contact / Q000276:immunology*; D005434:Flow Cytometry; D007801:Langerhans Cells / Q000276:immunology* / Q000378:metabolism; D037181:Lectins, C-Type / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D015778:Minor Histocompatibility Antigens; D011956:Receptors, Cell Surface / Q000378:metabolism; D012867:Skin / Q000276:immunology* / Q000378:metabolism
D015703:Antigens, CD; D001212:Asialoglycoproteins; D039481:CD11b Antigen; D039521:CD11c Antigen; D016827:CD8 Antigens; C431698:CD8alpha antigen; C064720:Clec10a protein, mouse; C093569:DEC-205 receptor; D037181:Lectins, C-Type; C464940:MGL2 protein, mouse; D008565:Membrane Proteins; D015778:Minor Histocompatibility Antigens; D011956:Receptors, Cell Surface