Syndecan-1 regulates dendritic cell migration in cutaneous hypersensitivity to haptens

被引:11
作者
Averbeck, Marco [1 ]
Kuhn, Stephanie [2 ]
Buehligen, Johannes [1 ]
Goette, Martin [3 ]
Simon, Jan C. [1 ]
Polte, Tobias [1 ,2 ]
机构
[1] Univ Klinikum Leipzig, Dept Dermatol Venerol & Allergol, Leipzig, Germany
[2] UFZ Helmholtz Ctr Environm Res Leipzig Halle, Dept Environm Immunol, Leipzig, Germany
[3] Munster Univ Hosp, Dept Gynecol & Obstet, Munster, Germany
关键词
cell migration; cutaneous hypersensitivity; dendritic cell; syndecan; HEPARAN-SULFATE; LANGERHANS CELLS; INTEGRIN; ADHESION; DISTINCT; GLYCOSAMINOGLYCANS; DEFICIENCY; EXPRESSION; MOTILITY;
D O I
10.1111/exd.13374
中图分类号
R75 [皮肤病学与性病学];
学科分类号
100206 ;
摘要
In human dendritic cells (DCs), we previously demonstrated in vitro that syndecan-1 (SDC1) is downregulated during maturation correlating with enhanced motility. We investigated the effects of SDC1 on DC migration in vivo during TNCB(2,4,6-trinitro-1-chlorobenzene)-induced cutaneous hypersensitivity reaction (CHS) in mice. We show that DC in SDC1-deficient mice migrated faster and at a higher rate to lymph nodes draining the hapten-painted skin. Adoptive transfer of SDC1-deficient hapten- and fluorochrome-labelled DC into wild-type (WT) mice led to increased and faster migration of DC to paracortical lymph nodes, and to a stronger CHS compared to WT DC. In SDC1-/- mice, CCR7 remains longer on the DC surface within the first 15-minutes maturation (after LPS-induced maturation). In addition, a time-dependent upregulation of CCL2, CCL3, VCAM1 and talin was found during maturation in SDC1-/- DC. However, no difference in T-cell-stimulating capacity of SDC1-deficient DC was found compared to WT DC. Mechanistically, SDC1-deficient DC showed enhanced migration towards CCL21 and CCL19. This may result from functional overexpression of CCR7 in SDC1-/- DC. Increased and accelerated migration of otherwise functionally intact SDC1-deficient DC leads to an exacerbated CHS. Based on our results, we conclude that SDC1 on DC negatively regulates DC migration.
引用
收藏
页码:1060 / 1067
页数:8
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