| First Author | Ito A | Year | 2016 |
| Journal | Immunity | Volume | 45 |
| Issue | 6 | Pages | 1311-1326 |
| PubMed ID | 28002731 | Mgi Jnum | J:257990 |
| Mgi Id | MGI:6112297 | Doi | 10.1016/j.immuni.2016.11.008 |
| Citation | Ito A, et al. (2016) Cholesterol Accumulation in CD11c(+) Immune Cells Is a Causal and Targetable Factor in Autoimmune Disease. Immunity 45(6):1311-1326 |
| abstractText | Liver X receptors (LXRs) are regulators of cholesterol metabolism that also modulate immune responses. Inactivation of LXR alpha and beta in mice leads to autoimmunity; however, how the regulation of cholesterol metabolism contributes to autoimmunity is unclear. Here we found that cholesterol loading of CD11c(+) cells triggered the development of autoimmunity, whereas preventing excess lipid accumulation by promoting cholesterol efflux was therapeutic. LXRbeta-deficient mice crossed to the hyperlipidemic ApoE-deficient background or challenged with a high-cholesterol diet developed autoantibodies. Cholesterol accumulation in lymphoid organs promoted T cell priming and stimulated the production of the B cell growth factors Baff and April. Conversely, B cell expansion and the development of autoantibodies in ApoE/LXR-beta-deficient mice was reversed by ApoA-I expression. These findings implicate cholesterol imbalance as a contributor to immune dysfunction and suggest that stimulating HDL-dependent reverse cholesterol transport could be beneficial in the setting of autoimmune disease. |
