| First Author | Raycroft MT | Year | 2012 |
| Journal | J Biol Chem | Volume | 287 |
| Issue | 8 | Pages | 5310-6 |
| PubMed ID | 22215667 | Mgi Jnum | J:182435 |
| Mgi Id | MGI:5315638 | Doi | 10.1074/jbc.M111.316356 |
| Citation | Raycroft MT, et al. (2012) Inhibition of antigen trafficking through scavenger receptor A. J Biol Chem 287(8):5310-6 |
| abstractText | B cell acquisition and presentation of specific autoantigens (auto-Ags) are thought to play an important and complex role in autoimmunity development. We previously identified scavenger receptor A (SR-A) as an early target in altering B cell-mediated autoimmunity. SR-A is highly expressed on professional antigen-presenting cells such as macrophages (MPhis) and dendritic cells (DCs). In this study, we demonstrate that SR-A is responsible for controlling B cell interactions with DCs/MPhis to promote Ag transfer from B cells to DCs/MPhis. We established a high-throughput ELISA-based screen to identify novel SR-A inhibitors, the specificity of which was determined by dose dependence and Biacore surface plasmon resonance testing. We identified small molecule inhibitors (SMIs) able to reduce SR-A-mediated Ag transfer in human cells. In particular, the SMIs prevented SR-A-positive cells from accumulating/loading Ag over time. Furthermore, we determined that one SMI, sennoside B, can reduce SR-A-mediated capture of B cells. Finally, SMI-mediated decreases in Ag transfer or accumulation reduced T cell proliferation in vitro and in vivo. These observations demonstrate that B cell-DC/MPhi interactions are conducive to promoting Ag trafficking between these cell types via SR-A. Inhibitors of SR-A may provide a novel therapeutic strategy in ameliorating autoimmune disease development. |
