Description:
<jats:title>Abstract</jats:title><jats:p>In human dendritic cells (<jats:styled-content style="fixed-case">DC</jats:styled-content>s), we previously demonstrated in vitro that syndecan‐1 (<jats:styled-content style="fixed-case">SDC</jats:styled-content>1) is downregulated during maturation correlating with enhanced motility.</jats:p><jats:p>We investigated the effects of <jats:styled-content style="fixed-case">SDC</jats:styled-content>1 on <jats:styled-content style="fixed-case">DC</jats:styled-content> migration in vivo during <jats:styled-content style="fixed-case">TNCB</jats:styled-content>(2,4,6‐trinitro‐1‐chlorobenzene)‐induced cutaneous hypersensitivity reaction (<jats:styled-content style="fixed-case">CHS</jats:styled-content>) in mice.</jats:p><jats:p>We show that <jats:styled-content style="fixed-case">DC</jats:styled-content> in <jats:styled-content style="fixed-case">SDC</jats:styled-content>1‐deficient mice migrated faster and at a higher rate to lymph nodes draining the hapten‐painted skin. Adoptive transfer of <jats:styled-content style="fixed-case">SDC</jats:styled-content>1‐deficient hapten‐ and fluorochrome‐labelled <jats:styled-content style="fixed-case">DC</jats:styled-content> into wild‐type (<jats:styled-content style="fixed-case">WT</jats:styled-content>) mice led to increased and faster migration of <jats:styled-content style="fixed-case">DC</jats:styled-content> to paracortical lymph nodes, and to a stronger <jats:styled-content style="fixed-case">CHS</jats:styled-content> compared to <jats:styled-content style="fixed-case">WT DC</jats:styled-content>. In <jats:styled-content style="fixed-case">SDC</jats:styled-content>1−/− mice, <jats:styled-content style="fixed-case">CCR</jats:styled-content>7 remains longer on the <jats:styled-content style="fixed-case">DC</jats:styled-content> surface within the first 15‐minutes maturation (after <jats:styled-content style="fixed-case">LPS</jats:styled-content>‐induced maturation). In addition, a time‐dependent upregulation of <jats:styled-content style="fixed-case">CCL</jats:styled-content>2, <jats:styled-content style="fixed-case">CCL</jats:styled-content>3, <jats:styled-content style="fixed-case">VCAM</jats:styled-content>1 and talin was found during maturation in <jats:styled-content style="fixed-case">SDC</jats:styled-content>1−/− <jats:styled-content style="fixed-case">DC</jats:styled-content>. However, no difference in T‐cell‐stimulating capacity of <jats:styled-content style="fixed-case">SDC</jats:styled-content>1‐deficient <jats:styled-content style="fixed-case">DC</jats:styled-content> was found compared to <jats:styled-content style="fixed-case">WT DC</jats:styled-content>. Mechanistically, <jats:styled-content style="fixed-case">SDC</jats:styled-content>1‐deficient <jats:styled-content style="fixed-case">DC</jats:styled-content> showed enhanced migration towards <jats:styled-content style="fixed-case">CCL</jats:styled-content>21 and <jats:styled-content style="fixed-case">CCL</jats:styled-content>19. This may result from functional overexpression of <jats:styled-content style="fixed-case">CCR</jats:styled-content>7 in <jats:styled-content style="fixed-case">SDC</jats:styled-content>1−/− <jats:styled-content style="fixed-case">DC</jats:styled-content>. Increased and accelerated migration of otherwise functionally intact <jats:styled-content style="fixed-case">SDC</jats:styled-content>1‐deficient <jats:styled-content style="fixed-case">DC</jats:styled-content> leads to an exacerbated <jats:styled-content style="fixed-case">CHS</jats:styled-content>. Based on our results, we conclude that <jats:styled-content style="fixed-case">SDC</jats:styled-content>1 on <jats:styled-content style="fixed-case">DC</jats:styled-content> negatively regulates <jats:styled-content style="fixed-case">DC</jats:styled-content> migration.</jats:p>