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Antiphospholipid antibodies induce translocation of TLR7 and TLR8 to the endosome in human monocytes and plasmacytoid dendritic cells
| Content Provider | Scilit |
|---|---|
| Author | Prinz, Nadine Clemens, Natascha Strand, Dennis Pütz, Inge Lorenz, Mareike Daiber, Andreas Stein, Pamela Degreif, Adriana Radsak, Markus Schild, Hansjörg Bauer, Stefan Landenberg, Philipp Von Lackner, Karl J. |
| Copyright Year | 2011 |
| Description | The antiphospholipid syndrome (APS) is an autoimmune disease characterized by thromboembolic events and/or fetal loss in the presence of antiphospholipid antibodies (aPLs). The mechanisms underlying the pathogenicity of aPLs are still poorly understood. Here we show that 3 human monoclonal aPLs as well as IgG fractions from patients with the APS increase mRNA expression of the intracellular toll-like receptor (TLR) 7 in plasmacytoid dendritic cells and TLR8 in monocytes. Simultaneously they induce the translocation of TLR7 or TLR8 from the endoplasmic reticulum to the endosome. These effects depend on the uptake of aPLs into the endosome, subsequent activation of endosomal NADPH oxidase, and generation of superoxide. As a consequence cells are dramatically sensitized to ligands for TLR7 and TLR8. This observation delineates a novel signal transduction pathway in innate immunity originating from the endosome. Because the overexpression of TLR7 can also be detected in plasmacytoid dendritic cells from patients with the APS ex vivo, our results provide an explanation for proinflammatory and procoagulant effects of aPLs. Because inappropriate expression of TLR7 has been implicated in the development of systemic autoimmunity, these findings may also be relevant for the understanding of autoimmunity. |
| Related Links | http://bloodjournal.hematologylibrary.org/content/118/8/2322.full.pdf |
| Ending Page | 2332 |
| Page Count | 11 |
| Starting Page | 2322 |
| DOI | 10.1182/blood-2011-01-330639 |
| Journal | Blood |
| Issue Number | 8 |
| Volume Number | 118 |
| Language | English |
| Publisher | American Society of Hematology |
| Publisher Date | 2011-08-25 |
| Access Restriction | Open |
| Subject Keyword | Research and Experimental Medicine Autoimmunity Endosome Monocytes Dendritic Cells Tlr7 Tlr8 Antibodies Antiphospholipid Induce Translocation Plasmacytoid Dendritic Journal: Blood (Vol- 105, Issue- 8) |
| Content Type | Text |
| Resource Type | Article |
