title: Apoptotic cells promote their own clearance and immune tolerance through activation of the nuclear receptor LXR.
abstract: Effective clearance of apoptotic cells by macrophages is essential for immune homeostasis. The transcriptional pathways that allow macrophages to sense and respond to apoptotic cells are poorly defined. We found that liver X receptor (LXR) signaling was important for both apoptotic cell clearance and the maintenance of immune tolerance. Apoptotic cell engulfment activated LXR and thereby induced the expression of Mer, a receptor tyrosine kinase critical for phagocytosis. LXR-deficient macrophages exhibited a selective defect in phagocytosis of apoptotic cells and an aberrant proinflammatory response to them. As a consequence of these defects, mice lacking LXRs manifested a breakdown in self-tolerance and developed autoantibodies and autoimmune glomerulonephritis. Treatment with an LXR agonist ameliorated disease progression in a mouse model of lupus-like autoimmunity. Thus, activation of LXR by apoptotic cells engages a virtuous cycle that promotes their own clearance and couples engulfment to the suppression of inflammatory pathways.
authors: Immune Signaling Laboratory, Department of Biochemistry and Molecular Biology, School of Medicine, University of Las Palmas, ULPGC, 35016 Las Palmas, Spain.
authors: Noelia
authors: N
authors: A-Gonzalez
authors: Steven J
authors: SJ
authors: Bensinger
authors: Cynthia
authors: C
authors: Hong
authors: Susana
authors: S
authors: Beceiro
authors: Michelle N
authors: MN
authors: Bradley
authors: Noam
authors: N
authors: Zelcer
authors: Jose
authors: J
authors: Deniz
authors: Cristina
authors: C
authors: Ramirez
authors: Mercedes
authors: M
authors: Díaz
authors: German
authors: G
authors: Gallardo
authors: Carlos Ruiz
authors: CR
authors: de Galarreta
authors: Jon
authors: J
authors: Salazar
authors: Felix
authors: F
authors: Lopez
authors: Peter
authors: P
authors: Edwards
authors: John
authors: J
authors: Parks
authors: Miguel
authors: M
authors: Andujar
authors: Peter
authors: P
authors: Tontonoz
authors: Antonio
authors: A
authors: Castrillo
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D001327:Autoimmune Diseases / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D015551:Autoimmunity / Q000276:immunology; D004268:DNA-Binding Proteins / Q000819:agonists* / Q000235:genetics / Q000276:immunology; D005786:Gene Expression Regulation / Q000235:genetics / Q000276:immunology; D007108:Immune Tolerance / Q000276:immunology; D000071518:Liver X Receptors; D008264:Macrophages / Q000166:cytology / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D057093:Orphan Nuclear Receptors; D010587:Phagocytosis / Q000276:immunology; D011518:Proto-Oncogene Proteins / Q000276:immunology / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000276:immunology / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists* / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology; D013154:Spleen / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D000076202:c-Mer Tyrosine Kinase
chemical_list: D004268:DNA-Binding Proteins; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D011518:Proto-Oncogene Proteins; D018160:Receptors, Cytoplasmic and Nuclear; C490767:Mertk protein, mouse; D020794:Receptor Protein-Tyrosine Kinases; D000076202:c-Mer Tyrosine Kinase