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

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

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1
Immune Signaling Laboratory, Department of Biochemistry and Molecular Biology, School of Medicine, University of Las Palmas, ULPGC, 35016 Las Palmas, Spain.

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.

PMID:
19646905
PMCID:
PMC2791787
DOI:
10.1016/j.immuni.2009.06.018
[Indexed for MEDLINE]
Free PMC Article

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