Ouwehand Krista, Santegoets Saskia J A M, Bruynzeel Derk P, Scheper Rik J, de Gruijl Tanja D, Gibbs Susan
Department of Dermatology, VU University Medical Centre, Amsterdam, The Netherlands.
Eur J Immunol. 2008 Nov;38(11):3050-9. doi: 10.1002/eji.200838384.
The initial step in Langerhans cell (LC) migration from the epidermis to the lymph node involves migration of maturing LC into the dermis. Here, we investigated the migration of LC out of the epidermis after exposure of the skin to contact allergens. Ex vivo intact human skin, epidermal sheets, and LC derived from the MUTZ-3 cell line (MUTZ-LC) were used to determine whether dermal fibroblasts play a role in mediating LC migration towards the dermis. Exposure of epidermal sheets or MUTZ-LC to allergens (nickel sulphate, 2,4-dinitrochlorobenzene, and cinnamaldehyde) or a cytokine maturation cocktail resulted in LC migration towards dermal fibroblasts. This was due to upregulation of CXCR4 on maturing LC and secretion of CXCL12/stromal derived factor-1 chemokine by fibroblasts. Neutralizing antibodies to either CXCL12 or CXCR4 completely blocked migration. Injection of CXCL12 neutralizing antibodies into intact human skin totally inhibited LC migration into the dermis. In contrast, neutralizing antibodies to CCL19/CCL21 did not inhibit migration into the dermis. We describe a novel and essential role of dermis-derived CXCL12 in initiating migration of maturing human LC to the dermis thus permitting their further journey to the draining lymph nodes.
朗格汉斯细胞（LC）从表皮迁移至淋巴结的初始步骤涉及成熟的LC迁移至真皮。在此，我们研究了皮肤接触变应原后LC从表皮迁出的情况。利用体外完整的人皮肤、表皮片以及源自MUTZ - 3细胞系的LC（MUTZ - LC）来确定真皮成纤维细胞在介导LC向真皮迁移过程中是否发挥作用。将表皮片或MUTZ - LC暴露于变应原（硫酸镍、2,4 - 二硝基氯苯和肉桂醛）或细胞因子成熟鸡尾酒会导致LC向真皮成纤维细胞迁移。这是由于成熟LC上CXCR4的上调以及成纤维细胞分泌CXCL12/基质细胞衍生因子 - 1趋化因子所致。针对CXCL12或CXCR4的中和抗体完全阻断了迁移。将CXCL12中和抗体注射到完整的人皮肤中完全抑制了LC向真皮的迁移。相比之下，针对CCL19/CCL21的中和抗体并未抑制向真皮的迁移。我们描述了真皮来源的CXCL12在启动成熟人LC向真皮迁移从而使其进一步前往引流淋巴结的过程中所起的新的重要作用。
