期刊
JOURNAL OF DERMATOLOGICAL SCIENCE
卷 74, 期 2, 页码 116-124出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.jdermsci.2013.12.013
关键词
VEGF; IL-17; gamma delta T cell; Plasmacytoid dendritic cell; Chemotaxis; Psoriasis
类别
资金
- Ministry of Education, Culture, Sports, Science and Technology in Japan
- Grants-in-Aid for Scientific Research [25293243] Funding Source: KAKEN
Background: IL-17-producing CD4+ T (Th17) cells and their cytokines, IL-17A and IL-22, are deeply involved in the pathogenesis of psoriasis by stimulating epidermal keratinocytes to proliferate and to produce cytokines/chemokines and vascular endothelial growth factor (VEGF)-A. Plasmacytoid dendritic cells (pDCs), infiltrating in psoriatic lesions, are known to exacerbate the Th17 -mediated pathogenesis of psoriasis. Objective: To address the initiative role of VEGF-A in the development of psoriasis and the pDC accumulation. Methods: Numerical changes and VEGF receptor 1 (VEGFR1) and VEGFR2 expressions were investigated in skin-infiltrating T cells and pDCs of K14-VEGF-A transgenic (Tg) and wild type (WT) mice. The chemotactic properties of VEGF-A for purified splenic pDCs were also evaluated by real-time chemotaxis assay. Results: By flow cytometry and immunohistochemistry, we observed that the number of dermal IL-17A(+) gamma delta T cells, but not CD4(+) T cells, was increased in VEGF-A Tg mice, suggesting that the main source of IL-17A was gamma delta T cells. Moreover, we identified pDCs as 440c(+) cells by immunohistochemistry and as PDCA-1(+)B220(+) cells by flow cytometry, and found that pDCs infiltrated at a higher frequency in VEGF-A Tg than WT mice. pDCs, but not gamma delta T cells, isolated from the skin expressed VEGFR1 and VEGFR2. Freshly isolated splenic pDCs expressed both receptors after 48-h cultivation. pDCs did not produce cytokines in response to VEGF-A, however, they had a strong velocity of chemotaxis toward VEGF-A at a comparable level to chemerin. Conclusions: These findings suggest that VEGF-A functions as not only a downstream enhancer but also an upstream initiator by chemoattracting pDCs in psoriatic lesions. (C) 2014 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据