The role of lipid-activated nuclear receptors in shaping macrophage and dendritic cell function: From physiology to pathology

Abstract

Nuclear receptors are ligand-activated transcription factors linking lipid signaling to the expression of the genome. There is increasing appreciation of the involvement of this receptor network in the metabolic programming of macrophages and dendritic cells (DCs), essential members of the innate immune system. In this review we focus on the role of retinoid X receptor, retinoic acid receptor, peroxisome proliferator-associated receptor γ, liver X receptor, and vitamin D receptor in shaping the immune and metabolic functions of macrophages and DCs. We also provide an overview of the contribution of macrophage- and DC-expressed nuclear receptors to various immunopathologic conditions, such as rheumatoid arthritis, inflammatory bowel disease, systemic lupus erythematosus, asthma, and some others. We suggest that systematic analyses of the roles of these receptors and their activating lipid ligands in immunopathologies combined with complementary and focused translational and clinical research will be crucial for the development of new therapies using the many molecules available to target nuclear receptors.

Keywords: 15-Deoxy-Δ12,14-prostaglandin J(2); 15d-PGJ(2); 9-Cis–retinoic acid; 9-cis-RA; ABC; AP-1; ATP-binding cassette; ATRA; Activator protein 1; All-trans-retinoic acid; BAL; Bronchoalveolar lavage; CIA; Collagen-induced arthritis; DBD; DC; DNA-binding domain; Dendritic cell; FDA; GALT; Gut-associated lymphoid tissue; HODE; Hydroxyoctadecadienoic acid; IBD; Inflammatory bowel disease; Invariant natural killer T; LBD; LPA; LXR; Ligand-binding domain; Liver X receptor; Lysophosphatidic acid; MMP; Macrophage; Matrix metalloproteinase; Oxidized low-density lipoprotein; PPAR; Peroxisome proliferator-associated receptor; Plasmacytoid dendritic cell; RA; RAR; RXR; Regulatory T; Retinoic acid receptor; Retinoid X receptor; Rheumatoid arthritis; SLE; STAT; Signal transducer and activator of transcription; Systemic lupus erythematosus; TLR; TZD; Thiazolidinedione; Toll-like receptor; Treg; US Food and Drug Administration; VDR; Vitamin D receptor; asthma; dendritic cell; iNKT; inflammatory bowel disease; lipid; liver X receptor; nuclear receptor; oxLDL; pDC; peroxisome proliferator-associated receptor; retinoic acid receptor; retinoid X receptor; rheumatoid arthritis; systemic lupus erythematosus; vitamin D receptor.