TY - JOUR
T1 - Apoptotic cells promote their own clearance and immune tolerance through activation of the nuclear receptor LXR
AU - A-Gonzalez, Noelia
AU - Bensinger, Steven J.
AU - Hong, Cynthia
AU - Beceiro, Susana
AU - Bradley, Michelle N.
AU - Zelcer, Noam
AU - Deniz, Jose
AU - Ramirez, Cristina
AU - Díaz, Mercedes
AU - Gallardo, German
AU - de Galarreta, Carlos Ruiz
AU - Salazar, Jon
AU - Lopez, Felix
AU - Edwards, Peter
AU - Parks, John
AU - Andujar, Miguel
AU - Tontonoz, Peter
AU - Castrillo, Antonio
PY - 2009
Y1 - 2009
N2 - 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
AB - 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
U2 - https://doi.org/10.1016/j.immuni.2009.06.018
DO - https://doi.org/10.1016/j.immuni.2009.06.018
M3 - Article
C2 - 19646905
SN - 1074-7613
VL - 31
SP - 245
EP - 258
JO - Immunity
JF - Immunity
IS - 2
ER -