Abstract：
:Psoriasis is a common chronic T-cell-mediated autoimmune skin disease, and traditional immunotherapies for psoriasis have focused on the direct inhibition of T cells, which often causes toxicity and lacks long-term effectiveness. Safe and effective therapeutic strategies are strongly needed for psoriasis. In this study, we show for the first time a significant accumulation of FLT3(+) CD11c(+) dendritic cells (DCs) in human psoriatic lesions and in the skin of experimental preclinical K14-VEGF transgenic homozygous mice, our animal model, although not an exact match for human psoriasis, displays many characteristics of inflammatory skin inflammation. SKLB4771, a potent and selective FLT3 inhibitor that we designed and synthesised, was used to treat cutaneous inflammation and psoriasis-like symptoms of disease in mice and almost completely cured the psoriasis-like disease without obvious toxicity. Mechanistic studies indicated that SKLB4771 treatment significantly decreased the number and activation of pDCs and mDCs in vitro and in vivo, and subsequent T-cell cascade reactions mediated by Th1/Th17 pathways. These findings show that targeted inhibition of FLT3, and hence direct interference with DCs, may be a novel therapeutic approach for the treatment of psoriasis.
journal_name
Immunol Resjournal_title
Immunologic researchauthors
Yan HX,Li WW,Zhang Y,Wei XW,Fu LX,Shen GB,Yin T,Li XY,Shi HS,Wan Y,Zhang QY,Li J,Yang SY,Wei YQdoi
10.1007/s12026-014-8521-4subject
Has Abstractpub_date
2014-10-01 00:00:00pages
112-26issue
1eissn
0257-277Xissn
1559-0755journal_volume
60pub_type
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