| First Author | Hannedouche S | Year | 2011 |
| Journal | Nature | Volume | 475 |
| Issue | 7357 | Pages | 524-7 |
| PubMed ID | 21796212 | Mgi Jnum | J:174682 |
| Mgi Id | MGI:5140625 | Doi | 10.1038/nature10280 |
| Citation | Hannedouche S, et al. (2011) Oxysterols direct immune cell migration via EBI2. Nature 475(7357):524-7 |
| abstractText | Epstein-Barr virus-induced gene 2 (EBI2, also known as GPR183) is a G-protein-coupled receptor that is required for humoral immune responses; polymorphisms in the receptor have been associated with inflammatory autoimmune diseases. The natural ligand for EBI2 has been unknown. Here we describe the identification of 7alpha,25-dihydroxycholesterol (also called 7alpha,25-OHC or 5-cholesten-3beta,7alpha,25-triol) as a potent and selective agonist of EBI2. Functional activation of human EBI2 by 7alpha,25-OHC and closely related oxysterols was verified by monitoring second messenger readouts and saturable, high-affinity radioligand binding. Furthermore, we find that 7alpha,25-OHC and closely related oxysterols act as chemoattractants for immune cells expressing EBI2 by directing cell migration in vitro and in vivo. A critical enzyme required for the generation of 7alpha,25-OHC is cholesterol 25-hydroxylase (CH25H). Similar to EBI2 receptor knockout mice, mice deficient in CH25H fail to position activated B cells within the spleen to the outer follicle and mount a reduced plasma cell response after an immune challenge. This demonstrates that CH25H generates EBI2 biological activity in vivo and indicates that the EBI2-oxysterol signalling pathway has an important role in the adaptive immune response. |
