Regulation of E-cadherin-mediated adhesion in langerhans cell-like dendritic cells by inflammatory mediators that mobilize Langerhans cells in vivo

Thilo Jakob, Mark C. Udey

Research output: Contribution to journalArticlepeer-review

140 Scopus citations

Abstract

Adhesion of Langerhans cells (LC) to keratinocytes is mediated by E- cadherin. IL-1, TNF-α, and LPS mobilize LC from epidermis and presumably attenuate LC-keratinocyte adhesion. To determine whether these mediators modulated LC E-cadherin-dependent adhesion directly, we characterized their effects on LC-like dendritic cells expanded from murine fetal skin (FSDDC). FSDDC were propagated from day 16 C57BL/6 fetal skin and isolated as aggregates (FSDDC-A) in which homophilic adhesion was mediated by E-cadherin. IL-1, TNF-α, and LPS induced dissociation of FSDDC-A that began within 4 to 8 h and was complete within 20 h. Anti-IL-1RI mAb inhibited disaggregation caused by IL-1α and IL-1β, but not that induced by TNF-α or LPS. Anti- TNF-α mAb inhibited the effect of TNF-α and LPS, but not that caused by IL- 1α or IL-1β. Flow cytometry of FSDDC-A revealed that IL-1, TNF-α, and LPS induced increased expression of MHC class II, CD40, and CD86 and decreased E- cadherin expression that was temporally related to dissociation of aggregates. IL-1 and TNF-α caused a rapid reduction in FSDDC E-cadherin mRNA levels that preceded the decrease in E-cadherin surface expression. These results demonstrate that cytokines that induce LC emigration in vivo act directly on LC-like cells in vitro, reduce E-cadherin mRNA levels, down- regulate E-cadherin surface expression, and induce a loss of E-cadherin- mediated adhesion.

Original languageEnglish
Pages (from-to)4067-4073
Number of pages7
JournalJournal of Immunology
Volume160
Issue number8
StatePublished - Apr 15 1998

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