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Published on: July 26, 2008
CD83 localization in a recycling compartment of immature human monocyte-derived dendritic cells
Elisabeth Klein1, Susanne Koch, Bodo Borm
1Department of Dermatology, Friedrich-Wilhelms-University of Bonn, Sigmund-Freud-Strasse 25, D-53105 Bonn, Germany.
Insights
Mature dendritic cells (DCs) show increased CD83 on their surface due to protein synthesis and regulated transport. CD83 localization shifts in mature DCs, involving endosomal proteases for cell surface exposure.
Area of Science:
- Immunology
- Cell Biology
Background:
- Dendritic cells (DCs) undergo significant phenotypic and functional changes during maturation.
- CD83 is a well-established surface marker for mature dendritic cells (mDCs).
Purpose of the Study:
- To investigate the intracellular localization and transport of CD83 in human monocyte-derived DCs.
- To elucidate the mechanisms regulating CD83 cell surface expression during DC maturation.
Main Methods:
- Analysis of intracellular CD83 localization in immature (iDC) and mature (mDC) human monocyte-derived DCs.
- Investigation of CD83 transport using endocytosis inhibitors and protease inhibitors.
Main Results:
- Enhanced CD83 surface expression in mDCs results from increased protein synthesis and regulated intracellular transport.
- CD83 is present in the Golgi and recycling endosomes in both iDCs and mDCs, but co-localizes with MHC class II in endocytic vesicles only in mDCs.
- Inhibition of endocytosis induced CD83 surface expression on iDCs, suggesting CD83 cycling.
- Protease inhibitors targeting thiol proteases and cathepsins impaired CD83 upregulation, indicating a role for endosomal proteases.
Conclusions:
- Regulated intracellular transport and endosomal protease activity are critical for maturation-induced CD83 surface expression on dendritic cells.
- CD83 exhibits dynamic intracellular trafficking and cycling between endosomes and the cell surface during DC maturation.
Abstract:
Dendritic cells (DC) change their phenotype and functional properties during maturation. CD83 cell surface expression is induced on mature DC (mDC). In this study, we investigated intracellular CD83 localization and transport in human monocyte-derived DC. The enhanced level of CD83 cell surface expression in mDC resulted predominantly from increased protein synthesis, and in addition from regulated intracellular transport of CD83 protein. An internal pool of CD83 protein is present in immature DC (iDC). Although CD83 protein in iDC and in mDC was localized in the Golgi compartment and in recycling endosomes, only in mature cells did CD83 co-localize with MHC class II molecules in endocytic vesicles. CD83 cell surface expression on iDC was induced by inhibition of endocytosis. This result could be explained by CD83 cycling between endosomes and the cell surface in iDC. The mDC also rapidly internalized membrane-bound CD83 protein. Furthermore, a thiol protease inhibitor and specific cathepsin inhibitors impaired CD83 up-regulation in DC, indicating a role of endosomal proteases in the maturation-induced exposure of CD83 on the plasma membrane.
