Title |
Accumulation of FLT3+ CD11c+ dendritic cells in psoriatic lesions and the anti-psoriatic effect of a selective FLT3 inhibitor
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Published in |
Immunologic Research, June 2014
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DOI | 10.1007/s12026-014-8521-4 |
Pubmed ID | |
Authors |
Heng-Xiu Yan, Wei-Wei Li, Yan Zhang, Xia-Wei Wei, Li-Xin Fu, Guo-Bo Shen, Tao Yin, Xiu-Ying Li, Hua-Shan Shi, Yang Wan, Qing-Yin Zhang, Jiong Li, Sheng-Yong Yang, Yu-Quan Wei |
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. |
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Geographical breakdown
Country | Count | As % |
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Germany | 1 | 50% |
United Kingdom | 1 | 50% |
Demographic breakdown
Type | Count | As % |
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Members of the public | 1 | 50% |
Science communicators (journalists, bloggers, editors) | 1 | 50% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
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Unknown | 23 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
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Researcher | 10 | 43% |
Student > Master | 3 | 13% |
Student > Bachelor | 2 | 9% |
Student > Doctoral Student | 2 | 9% |
Student > Ph. D. Student | 2 | 9% |
Other | 0 | 0% |
Unknown | 4 | 17% |
Readers by discipline | Count | As % |
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Medicine and Dentistry | 7 | 30% |
Agricultural and Biological Sciences | 5 | 22% |
Biochemistry, Genetics and Molecular Biology | 4 | 17% |
Pharmacology, Toxicology and Pharmaceutical Science | 2 | 9% |
Computer Science | 1 | 4% |
Other | 0 | 0% |
Unknown | 4 | 17% |