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Title

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

AuthorsGonzález, Noelia A.; Bensinger, Steven J.; Díaz, Mercedes; Tontonoz, Peter; Castrillo, Antonio CSIC
Issue Date30-Jul-2009
PublisherElsevier
CitationImmunity 31(2): 245-258 (2009)
AbstractEffective 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 ina 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.
Description14 pages, 7 figures.-- El pdf del artículo es el manuscrito de autor.-- et al.
Supporting information available at: http://www.cell.com/immunity/supplemental/S1074-7613(09)00318-5
Publisher version (URL)http://dx.doi.org/10.1016/j.immuni.2009.06.018
URIhttp://hdl.handle.net/10261/15571
DOI10.1016/j.immuni.2009.06.018
ISSN1074-7613
Appears in Collections:(IIBM) Artículos




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