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

Abstract

In human dendritic cells (DC), 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 min maturation (or: after LPS-induced maturation). In addition, a time-dependent up-regulation 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.

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