Apoptotic cells promote their own clearance and immune tolerance through activation of the nuclear receptor LXR.
Apoptotic cells promote their own clearance and immune tolerance through activation of the nuclear receptor LXR.
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DOI：
10.1016/j.immuni.2009.06.018
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发表时间：
2009-08-21
期刊：
影响因子：
32.4
通讯作者：
Castrillo, Antonio
中科院分区：
文献类型：
--
作者：
A-Gonzalez, Noelia;Bensinger, Steven J.;Hong, Cynthia;Beceiro, Susana;Bradley, Michelle N.;Zelcer, Noam;Deniz, Jose;Ramirez, Cristina;Diaz, Mercedes;Gallardo, German;Ruiz de Galarreta, Carlos;Salazar, Jon;Lopez, Felix;Edwards, Peter;Parks, John;Andujar, Miguel;Tontonoz, Peter;Castrillo, Antonio
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 demonstrate here that LXR signaling is important for both apoptotic cell clearance and the maintenance of immune tolerance. Apoptotic cell engulfment activates LXR and thereby induces the expression of Mer, a receptor tyrosine kinase critical for phagocytosis. LXR null macrophages exhibit a selective defect in phagocytosis of apoptotic cells and an aberrant pro-inflammatory response to them. As a consequence of these defects, mice lacking LXRs manifest a breakdown in self-tolerance and develop autoantibodies and autoimmune glomerulonephritis. Treatment with an LXR agonist ameliorates disease progression in mouse models 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.
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