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An Efficient and High Yield Method for Isolation of Mouse Dendritic Cell Subsets
Published on: April 18, 2016
The soluble form of CD83 dramatically changes the cytoskeleton of dendritic cells
Nicole Kotzor1, Matthias Lechmann, Elisabeth Zinser
1Department of Dermatology, University Hospital Erlangen, Hartmannstr. 14, D-91052 Erlangen, Germany.
Insights
Soluble CD83 inhibits dendritic cell (DC) maturation and T cell proliferation. This soluble form alters the DC cytoskeleton, preventing T cell clustering and immune stimulation.
Area of Science:
- Immunology
- Cell Biology
Background:
- CD83 is a key marker for mature dendritic cells (DCs).
- A soluble form of CD83 inhibits DC maturation and T cell proliferation.
- CD83 shedding occurs during viral infections and is elevated in hematological malignancies.
Purpose of the Study:
- To elucidate the molecular mechanism by which soluble CD83 impacts DC function.
- To investigate the effect of soluble CD83 on the DC cytoskeleton and T cell interactions.
Main Methods:
- Mature DCs were treated with soluble CD83 at 10 microg/ml.
- Cytoskeletal changes were analyzed using phalloidin, tubulin, and fascin antibodies.
- DC-T cell clustering and T cell stimulation were assessed.
Main Results:
- Soluble CD83 treatment caused DCs to round up, with altered or absent veils.
- Significant changes in the DC cytoskeleton were observed.
- Soluble CD83 completely inhibited DC-T cell clustering, a prerequisite for T cell stimulation.
Conclusions:
- Soluble CD83 disrupts the DC cytoskeleton, impairing their ability to interact with and stimulate T cells.
- This finding provides a molecular mechanism for soluble CD83's immunomodulatory effects.
Abstract:
CD83 is the best-known surface marker for mature dendritic cells (DC) and recently we could show that a soluble form of CD83 inhibits DC maturation. In addition, this soluble form inhibits DC-mediated T cell proliferation in vitro and in vivo. Furthermore, several viruses induce CD83 degradation or shedding in infected DC. A soluble form of CD83 was also found in plasma and serum of healthy individuals and interestingly at highly elevated levels in a number of haematological malignancies. Thus, CD83 also has functional implications for the immune response. However, the molecular mechanism is not well defined. Here we describe for the first time that soluble CD83 completely changed the cytoskeleton (analysed using phalloidin-, tubulin- and fascin-specific antibodies) when administered at a concentration of 10 microg/ml to mature DC. The cells rounded off and had only short, truncated, or no veils at all. Furthermore, soluble CD83-treated cells were completely inhibited in their ability to form clusters with T cells, an absolute prerequisite in order to stimulate T cells.
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