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Abstracts (complete list) - Wissenschaft Online

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Andrea Mahr<br />

Suppression of Dendritic Cell Activation by Annexin 1<br />

on the Surface of Apoptotic Cells<br />

Dendritic cells (DCs) are phagocytic cells that discriminate “non-self” from “self”<br />

structures, and consequently initiate immunity or tolerance. Pathogenic components,<br />

like bacteria-derived lipopolysaccharide (LPS), are recognized by Toll-Like Receptors<br />

(TLRs) on the surface of DCs, leading to DC activation and secretion of proinflammatory<br />

cytokines. This process can be inhibited by the uptake of apoptotic cells, the biggest<br />

source of “self”-material. Inhibition is probably mediated by tolerogenic signals on the<br />

surface of apoptotic cells, but the molecules relevant for this process are not yet well<br />

defined. A candidate protein is annexin 1, which is externalized by early apoptotic cells.<br />

In this study, it has been found that pre-incubation of DCs with apoptotic cells or<br />

purified recombinant annexin 1 before TLR stimulation could reduce the transcriptional<br />

upregulation and secretion of proinflammatory cytokines.<br />

Correspondingly, annexin 1 led to a substantial decrease of LPS-induced TLR signal<br />

transduction.<br />

The detailed analysis of annexin 1 function may lead to a more advanced understanding<br />

of the regulation of TLR signaling, and would give valuable insight into a potential<br />

mechanism of peripheral non-responsiveness.

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