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Immunity. 2012 May 25;36(5):834-46. doi: 10.1016/j.immuni.2012.03.010. Epub 2012 Apr 12.

12/15-lipoxygenase orchestrates the clearance of apoptotic cells and maintains immunologic tolerance.

Author information

1
Department of Internal Medicine 3 and Institute for Clinical Immunology, University of Erlangen-Nuremberg, 91054 Erlangen, Germany.

Abstract

Noninflammatory clearance of apoptotic cells (ACs) is crucial to maintain self-tolerance. Here, we have reported a role for the enzyme 12/15-lipoxygenase (12/15-LO) as a central factor governing the sorting of ACs into differentially activated monocyte subpopulations. During inflammation, uptake of ACs was confined to a population of 12/15-LO-expressing, alternatively activated resident macrophages (resMΦ), which blocked uptake of ACs into freshly recruited inflammatory Ly6C(hi) monocytes in a 12/15-LO-dependent manner. ResMΦ exposed 12/15-LO-derived oxidation products of phosphatidylethanolamine (oxPE) on their plasma membranes and thereby generated a sink for distinct soluble receptors for ACs such as milk fat globule-EGF factor 8, which were essential for the uptake of ACs into inflammatory monocytes. Loss of 12/15-LO activity, in turn, resulted in an aberrant phagocytosis of ACs by inflammatory monocytes, subsequent antigen presentation of AC-derived antigens, and a lupus-like autoimmune disease. Our data reveal an unexpected key role for enzymatic lipid oxidation during the maintenance of self-tolerance.

PMID:
22503541
DOI:
10.1016/j.immuni.2012.03.010
[Indexed for MEDLINE]
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