Department of Dermatology, Huazhong University of Science and Technology, Wuhan, China.
Eur J Dermatol. 2011 Sep-Oct;21(5):731-6. doi: 10.1684/ejd.2011.1469.
Mononuclear cell (MNC) infiltrate is one of the earliest pathological changes in systemic sclerosis (SSc) skin. However, little is known about the recruitment of these cells into skin lesions. Recently, the role of chemokines has been suggested in the pathogenesis of SSc. Here we studied the expressions and distributions of CC chemokine CCL20 and its receptor CCR6 in early SSc skin lesions and the difference in CCL20 expressions and ability to recruite MNCs of normal dermal fibroblast (NDF) and scleroderma dermal fibroblast (SSDF). We found that the expressions of CCL20 and its receptor CCR6 were obviously up-regulated in SSc in contrast to normal human skin. mRNA levels were significantly expressed in SSc lesional skins vs normal skin tissues. SSDF displayed increased constitutive expressions of CCL20 mRNA and protein. In addition, Th1 cytokines (TNF-α and IL-1β) remarkably increased the expression of CCL20 in both NDF and SSDF in a dose- and time-dependent manner. Supernatants from SSDF showed stronger chemotactic activity to PBMCs than those from NDF. Thus our findings suggest that CCL20 released from cytokine-activated SSDF plays an important role in the induction of SSc by further recruiting more MNCs to the skin.
单核细胞（MNC）浸润是系统性硬化症（SSc）皮肤的最早病理变化之一。然而，对于这些细胞如何招募到皮肤病变部位，我们知之甚少。最近，趋化因子在 SSc 的发病机制中的作用已被提出。在这里，我们研究了 CC 趋化因子 CCL20 及其受体 CCR6 在早期 SSc 皮肤病变中的表达和分布，以及正常真皮成纤维细胞（NDF）和硬皮病真皮成纤维细胞（SSDF）的 CCL20 表达和招募 MNC 的能力差异。我们发现 CCL20 及其受体 CCR6 的表达在 SSc 中明显上调，与正常人皮肤相比。与正常皮肤组织相比，mRNA 水平在 SSc 病变皮肤中明显表达。SSDF 显示出 CCL20 mRNA 和蛋白的组成性表达增加。此外，Th1 细胞因子（TNF-α和 IL-1β）以剂量和时间依赖的方式显著增加了 NDF 和 SSDF 中 CCL20 的表达。来自 SSDF 的上清液对 PBMC 的趋化活性强于来自 NDF 的上清液。因此，我们的研究结果表明，由细胞因子激活的 SSDF 释放的 CCL20 通过进一步招募更多的 MNC 到皮肤中，在 SSc 的诱导中发挥重要作用。
