Effects of solar ultraviolet radiation on engineered human skin equivalent containing both langerhans cells and dermal dendritic cells

被引:67
作者
Bechetoille, Nicolas
Dezutter-Dambuyant, Colette
Damour, Odile
Andre, Valerie
Orly, Isabelle
Perrier, Eric
机构
[1] Colet Engelhard BASF, F-69007 Lyon, France
[2] Univ Lyon 1, Equipe Accueil, Lyon, France
[3] Hop Edouard Herriot, Banque Tissus & Cellules, Lyon, France
来源
TISSUE ENGINEERING | 2007年 / 13卷 / 11期
关键词
D O I
10.1089/ten.2006.0405
中图分类号
Q813 [细胞工程];
学科分类号
摘要
Exposure of human skin to solar ultraviolet (UV) light induces local and systemic immune suppression. It is known that alterations of immune functions of Langerhans cells (LCs) and dermal dendritic cells (DDCs) mediate this phenomenon. The purpose of this study was to mimic in vitro the early UV-induced skin disruption to better understand the involvement of the skin micro-environment in triggering this immunosuppressive state. We therefore developed skin equivalents (SEs) integrating LCs and DDCs derived from monocytes (mo-LCs and mo-DDCs, respectively). First, we showed that Langerin(+) mo-LC and dendritic cell (DC)-specific ICAM-3 grabbing nonintegrin (SIGN)(+) mo-DDCs were immunolocalized in situ in epidermal and dermal compartments of SEs, respectively. The SE micro-environment without immune cells displayed full cytokine profile that may ensure and maintain differentiation, localization, and immaturity of LCs and DDCs in situ, as shown by secretion of granulocyte-macrophage colony stimulating factor, transforming growth factor beta (beta)-1, interleukin (IL)-4, IL-13, and IL-15 involved in cell differentiation; presence of complete chemokine network as macrophage inflammatory protein 3 alpha (alpha); low secretion of pro-inflammatory cytokines tumor necrosis factor alpha (TNF-alpha), IL-1 beta, IL-6, and IL-8; and surprising secretion of immunosuppresive cytokine IL-10. Second, we demonstrated that skin micro-environment homeostasis was greatly disrupted under solar UV irradiation of SEs. In fact, we showed a pro-inflammatory state characterized by high secretion of TNF-alpha, IL-1 beta, IL-6, and IL-8 and low secretion of IL-10. This breakdown of immune homeostasis was visualized at the same time as in situ migration of mo-LCs and mo-DDCs into the dermal equivalent of SEs. Moreover, this tissue migration of mo-LCs and mo-DDCs into SEs was in accordance with the chemokine (C-C motif) receptor 7 expression and the DC-lysosome-associated membrane glycoprotein acquisition only on mo-LCs. Our results highlighted major participation of the skin micro-environment in the triggering and modulating of UV-induced skin immune responses. In addition, it could be concluded that these SEs are reliable tools for modeling biological events inaccessible in humans.
引用
收藏
页码:2667 / 2679
页数:13
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