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

In human dendritic cells ( DC s), we previously demonstrated in vitro that syndecan‐1 ( SDC 1) is downregulated during maturation correlating with enhanced motility. We investigated the effects of SDC 1 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 SDC 1‐deficient mice migrated faster and at a higher rate to lymph nodes draining the hapten‐painted skin. Adoptive transfer of SDC 1‐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 SDC 1−/− mice, CCR 7 remains longer on the DC surface within the first 15‐minutes maturation (after LPS ‐induced maturation). In addition, a time‐dependent upregulation of CCL 2, CCL 3, VCAM 1 and talin was found during maturation in SDC 1−/− DC . However, no difference in T‐cell‐stimulating capacity of SDC 1‐deficient DC was found compared to WT DC . Mechanistically, SDC 1‐deficient DC showed enhanced migration towards CCL 21 and CCL 19. This may result from functional overexpression of CCR 7 in SDC 1−/− DC . Increased and accelerated migration of otherwise functionally intact SDC 1‐deficient DC leads to an exacerbated CHS . Based on our results, we conclude that SDC 1 on DC negatively regulates DC migration.