Immunologic Research

, Volume 60, Issue 1, pp 112–126

Accumulation of FLT3+ CD11c+ dendritic cells in psoriatic lesions and the anti-psoriatic effect of a selective FLT3 inhibitor

  • 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
Article

DOI: 10.1007/s12026-014-8521-4

Cite this article as:
Yan, HX., Li, WW., Zhang, Y. et al. Immunol Res (2014) 60: 112. doi:10.1007/s12026-014-8521-4

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.

Keywords

FLT3+ CD11c+ DCs FLT3 inhibitor Immunotherapy Psoriasis 

Supplementary material

12026_2014_8521_MOESM1_ESM.tif (80 kb)
Supplement Fig 1Inhibition of FLT3+CD11c+precursorin bone marrow by SKLB4771 treatment in vivo. Flow cytometric quantification of FLT3+ CD11c+ precursor in bone marrow isolated from vehicle-treated psoriatic plaque lesions and SKLB4771-treated lesions. The number of decreased in psoriatic plaque lesions of SKLB4771-treated mice when compared with vehicle-treated mice (mean ± S.D., n = 6 per group). Ordinates in the histogram indicate the percentage of FLT3+ CD11c+ precursor within total cells. Data are representative of three independent experiments. (TIFF 80 kb)
12026_2014_8521_MOESM2_ESM.tif (232 kb)
Supplement Fig 2 Inhibition of IL-12p70 by SKLB4771 treatment in vivo. Homogenised ear tissues from SKLB4771- or vehicle-treated groups were investigated by ELISA. The amount of IL-12p70 was found to be significantly decreased in SKLB4771-treated mice (mean ± S.D., n = 3 per group). (TIFF 232 kb)
12026_2014_8521_MOESM3_ESM.doc (56 kb)
Supplementary material 3 (DOC 56 kb)

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Heng-Xiu Yan
    • 1
    • 2
  • Wei-Wei Li
    • 1
    • 4
  • Yan Zhang
    • 1
  • Xia-Wei Wei
    • 1
  • Li-Xin Fu
    • 2
  • Guo-Bo Shen
    • 1
  • Tao Yin
    • 1
  • Xiu-Ying Li
    • 1
  • Hua-Shan Shi
    • 1
  • Yang Wan
    • 1
  • Qing-Yin Zhang
    • 3
  • Jiong Li
    • 1
  • Sheng-Yong Yang
    • 1
  • Yu-Quan Wei
    • 1
  1. 1.State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical SchoolSichuan UniversityChengduChina
  2. 2.College of Life Science and TechnologySouthwest University for NationalitiesChengduChina
  3. 3.Department of Dermatovenereology, West China HospitalSichuan UniversityChengduChina
  4. 4.Department of Pharmacy, Xijing HospitalFourth Military UniversityXi’anChina

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