Apoptotic cells promote their own clearance and immune tolerance through activation of the nuclear receptor LXR

Immunity. 2009 Aug 21;31(2):245-58. doi: 10.1016/j.immuni.2009.06.018. Epub 2009 Jul 30.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / immunology*
  • Autoimmune Diseases / immunology*
  • Autoimmune Diseases / metabolism
  • Autoimmune Diseases / pathology
  • Autoimmunity / immunology
  • DNA-Binding Proteins / agonists*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / immunology
  • Gene Expression Regulation / genetics
  • Gene Expression Regulation / immunology
  • Immune Tolerance / immunology
  • Liver X Receptors
  • Macrophages / cytology
  • Macrophages / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Orphan Nuclear Receptors
  • Phagocytosis / immunology
  • Proto-Oncogene Proteins / immunology
  • Proto-Oncogene Proteins / metabolism
  • Receptor Protein-Tyrosine Kinases / immunology
  • Receptor Protein-Tyrosine Kinases / metabolism
  • Receptors, Cytoplasmic and Nuclear / agonists*
  • Receptors, Cytoplasmic and Nuclear / genetics
  • Receptors, Cytoplasmic and Nuclear / immunology
  • Signal Transduction / immunology
  • Spleen / cytology
  • Spleen / immunology*
  • Spleen / metabolism
  • c-Mer Tyrosine Kinase


  • DNA-Binding Proteins
  • Liver X Receptors
  • Orphan Nuclear Receptors
  • Proto-Oncogene Proteins
  • Receptors, Cytoplasmic and Nuclear
  • Mertk protein, mouse
  • Receptor Protein-Tyrosine Kinases
  • c-Mer Tyrosine Kinase

Associated data

  • GEO/GSE17088