CXCL12 is essential for migration of activated Langerhans cells from epidermis to dermis

被引：99
作者：
Ouwehand, Krista [1 ]
Santegoets, Saskia J. A. M. [2 ]
Bruynzeel, Derk P. [1 ]
Scheper, Rik J. [2 ]
de Gruijl, Tanja D. [3 ]
Gibbs, Susan [1 ]
机构：
[1] Vrije Univ Amsterdam Med Ctr, Dept Dermatol, Amsterdam, Netherlands
[2] Vrije Univ Amsterdam Med Ctr, Dept Pathol, Amsterdam, Netherlands
[3] Vrije Univ Amsterdam Med Ctr, Dept Med Oncol, Amsterdam, Netherlands
来源：
EUROPEAN JOURNAL OF IMMUNOLOGY | 2008年 / 38卷 / 11期
关键词：
Allergy; Chemotaxis; Cytokines; DC; Skin;
D O I：
10.1002/eji.200838384
中图分类号：
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号：
100102 ;
摘要：
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.
引用
收藏
页码：3050 / 3059
页数：10
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