Tn antigen suppresses lipopolysaccharide-induced dermatitis via Clec10a.

C-type lectin domain family 10 member A (Clec10a), also called macrophage galactose-type lectin 1 (MGL1) or CD301a, is expressed on myeloid cells, including macrophages in the skin. Several pieces of evidence suggest that Clec10a physically binds to O-linked mucin-like molecules, but the functional ligand that mediates signaling in macrophages remains undetermined. We previously reported that house dust mite (HDM) treatment on the skin produced a greater amount of Toll-like receptor 4 (TLR4)-mediated inflammatory cytokines from macrophage in Clec10a-deficient mice than in wild-type (WT) mice, suggesting that a functional ligand for Clec10a contained in HDM inhibited TLR4-mediated skin macrophage activation. In this study, we investigated the glycan structure of a functional Clec10a ligand (Clec10a-L) contained in HDM. We showed that Clec10a bound to O-linked mucin-like molecules such as polyacrylamide (PAA)-conjugated Tn antigen (Tn antigen-PAA), Core1-PAA, LacNAc-PAA, Lewis A-PAA, and Lewis X-PAA. Among them, plate-coated Tn antigen-PAA, Lewis A-PAA, and Lewis X-PAA activated Clec10a expressed on the reporter cells. However, intradermal injection of only Tn antigen-PAA, but not Lewis A-PAA and Lewis X-PAA, ameliorated LPS-induced dermatitis in WT but not Clec10a-deficient mice. Moreover, Tn antigen-PAA suppressed LPS-induced production of inflammatory cytokines IL-6 and TNF-α by bone marrow-derived cultured macrophage in vitro. These results indicate that Tn antigen is a functional Clec10a-L in HDM that suppresses TLR4-induced macrophage activation in the skin.