Uderhardt S, Herrmann M, Oskolkova OV, Aschermann S, Bicker W, Ipseiz N, Sarter-Zaiss K, Frey B, Rothe T, Voll R, Nimmerjahn F, Bochkov VN, Schett G, Krönke G (2012)
Publication Status: Published
Publication Type: Journal article
Publication year: 2012
Book Volume: 36
Pages Range: 834-46
Journal Issue: 5
DOI: 10.1016/j.immuni.2012.03.010
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.
APA:
Uderhardt, S., Herrmann, M., Oskolkova, O.V., Aschermann, S., Bicker, W., Ipseiz, N.,... Krönke, G. (2012). 12/15-lipoxygenase orchestrates the clearance of apoptotic cells and maintains immunologic tolerance. Immunity, 36(5), 834-46. https://doi.org/10.1016/j.immuni.2012.03.010
MLA:
Uderhardt, Stefan, et al. "12/15-lipoxygenase orchestrates the clearance of apoptotic cells and maintains immunologic tolerance." Immunity 36.5 (2012): 834-46.
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