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Title: Cholesterol accumulation in CD11c+ immune cells is a causal and targetable factor in autoimmune disease
Authors: Ito, Ayaka
Hong, Cynthia
Oka, Kazuhiro
Salazar, Jon V.
Diehl, Cody
Witztum, Joseph L.
Díaz-Sarmiento, Mercedes 
Castrillo Viguera, Antonio 
Bensinger, Steven J.
Chan, Lawrence
Tontonoz, Peter
UNESCO Clasification: 32 Ciencias médicas
320710 Inmunopatología
Issue Date: 2016
Journal: Immunity 
Abstract: 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. LXR beta-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.
ISSN: 1074-7613
DOI: 10.1016/j.immuni.2016.11.008
Source: Immunity [ISSN 1074-7613], v. 45 (6), p. 1311-1326
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