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- W2079590189 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." @default.
- W2079590189 created "2016-06-24" @default.
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- W2079590189 date "2012-05-01" @default.
- W2079590189 modified "2023-10-16" @default.
- W2079590189 title "12/15-Lipoxygenase Orchestrates the Clearance of Apoptotic Cells and Maintains Immunologic Tolerance" @default.
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- W2079590189 doi "https://doi.org/10.1016/j.immuni.2012.03.010" @default.
- W2079590189 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/22503541" @default.
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