| First Author | Li N | Year | 2024 |
| Journal | Biochim Biophys Acta Mol Basis Dis | Volume | 1870 |
| Issue | 2 | Pages | 166988 |
| PubMed ID | 38070583 | Mgi Jnum | J:343757 |
| Mgi Id | MGI:7569941 | Doi | 10.1016/j.bbadis.2023.166988 |
| Citation | Li N, et al. (2024) Fucosylation deficiency enhances imiquimod-induced psoriasis-like skin inflammation by promoting CXCL1 expression. Biochim Biophys Acta Mol Basis Dis 1870(2):166988 |
| abstractText | Psoriasis is a multifaceted chronic inflammatory skin disease; however, its underlying molecular mechanisms remain unclear. In this study, we explored the role of fucosylation in psoriasis using an imiquimod-induced psoriasis-like mouse model. ABH antigen and fucosyltransferase 1 (Fut1) expression was reduced in the granular layer of lesional skin of patients with psoriasis. In particular, the blood group H antigen type 2 (H2 antigen)-a precursor of blood group A and B antigens-and FUT1 were highly expressed throughout the spinous layer in both patients with psoriasis and the skin of imiquimod-treated mice. Upon the application of imiquimod, Fut1-deficient mice, which lacked the H2 antigen, exhibited higher clinical scores based on erythema, induration, and scaling than those of wild-type mice. Imiquimod-treated Fut1-deficient mice displayed increased skin thickness, trans-epidermal water loss, and Gr-1(+) cell infiltration compared with wild-type mice. Notably, the levels of CXCL1 protein and mRNA were significantly higher in Fut1-deficient mice than those in wild-type mice; however, there were no significant differences in other psoriasis-related markers, such as IL-1beta, IL-6, IL-17A, and IL-23. Fut1-deficient primary keratinocytes treated with IL-17A also showed a significant increase in both mRNA and protein levels of CXCL1 compared with IL-17A-treated wild-type primary keratinocytes. Further mechanistic studies revealed that this increased Cxcl1 mRNA in Fut1-deficient keratinocytes was caused by enhanced Cxcl1 mRNA stabilization. In summary, our findings indicated that fucosylation, which is essential for ABH antigen synthesis in humans, plays a protective role in psoriasis-like skin inflammation and is a potential therapeutic target for psoriasis. |
