Angel Catherine E, Lala Aisha, Chen Chun-Jen J, Edgar Stephen G, Ostrovsky Lena L, Dunbar P Rod
School of Biological Sciences, University of Auckland, Auckland, New Zealand.
Int Immunol. 2007 Nov;19(11):1271-9. doi: 10.1093/intimm/dxm096. Epub 2007 Sep 5.
We recently demonstrated that three antigen-presenting cell (APC) subsets exist in the healthy human dermis, CD14(+) and CD1a(+) dermal APCs and migratory dermal Langerhans cells. Here, we extend these findings by defining CD208 as an exclusive marker of migratory dermal Langerhans cells, confirming that migratory dermal Langerhans cells (CD1a(high) CD207(+) CD208(+)) and CD1a(+) dermal APCs (CD1a(mid) CD207(-) CD208(-)) are two distinct APC populations. Using flow cytometry and multicolor fluorescence immunohistochemistry, we demonstrated that there were striking differences between CD1a(+) and CD14(+) dermal APCs in their expression of pattern recognition receptors and maturation markers. Expression of Toll-like receptor (TLR) 2, CD206 and CD209 was largely restricted to CD14(+) dermal APCs. Consistent with these observations, most CD14(+) dermal APCs expressed an immature phenotype when compared with CD1a(+) dermal APCs, which expressed high levels of the maturation marker CD83 on their cell surface. However, a subset of CD14(+) dermal APCs also expressed cell-surface CD83, associated with a loss of cell-surface TLR2, suggesting that they have the capacity to mature. CD14(+) dermal APCs are therefore the dominant cutaneous APC population capable of sensing ligands recognized by CD206, CD209 and TLR2 and subsequently may have the potential to mature. CD68 expression was largely restricted to a subset of CD14(+) dermal APCs, while both CD14(+) and CD1a(+) dermal APCs expressed CD11b and CD11c. These findings have important implications for understanding cutaneous immune responses in humans and for the optimization of vaccine delivery via the skin.
我们最近证明，在健康人的真皮中存在三种抗原呈递细胞（APC）亚群，即CD14(+)和CD1a(+)真皮APC以及迁移性真皮朗格汉斯细胞。在此，我们通过将CD208定义为迁移性真皮朗格汉斯细胞的唯一标志物来扩展这些发现，证实迁移性真皮朗格汉斯细胞（CD1a(高) CD207(+) CD208(+)）和CD1a(+)真皮APC（CD1a(中) CD207(-) CD208(-)）是两个不同的APC群体。使用流式细胞术和多色荧光免疫组织化学，我们证明CD1a(+)和CD14(+)真皮APC在模式识别受体和成熟标志物的表达上存在显著差异。Toll样受体（TLR）2、CD206和CD209的表达主要局限于CD14(+)真皮APC。与这些观察结果一致，与表达高水平成熟标志物CD83的CD1a(+)真皮APC相比，大多数CD14(+)真皮APC表现出未成熟的表型。然而，一部分CD14(+)真皮APC也表达细胞表面CD83，这与细胞表面TLR2的丧失相关，表明它们具有成熟的能力。因此，CD14(+)真皮APC是能够感知由CD206、CD209和TLR2识别的配体并随后可能具有成熟潜力的主要皮肤APC群体。CD68的表达主要局限于CD14(+)真皮APC的一个亚群，而CD14(+)和CD1a(+)真皮APC均表达CD11b和CD11c。这些发现对于理解人类皮肤免疫反应以及优化经皮疫苗递送具有重要意义。
