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

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

Journal

Immunity Elsevier

Book Volume: 36

Pages Range: 834-46

Journal Issue: 5

DOI: 10.1016/j.immuni.2012.03.010

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.

Authors with CRIS profile

Martin Herrmann Department of Medicine 3 – Rheumatology and Immunology Susanne Aschermann Lehrstuhl für Genetik Kerstin Sarter-Zaiss Department of Medicine 3 – Rheumatology and Immunology Benjamin Frey Department of Radiation Oncology Falk Nimmerjahn Lehrstuhl für Genetik Georg Schett Lehrstuhl für Innere Medizin III Gerhard Krönke Professur für Translationale Immunologie

Involved external institutions

Medizinische Universität Wien AT Austria (AT) Forensisch-Toxikologisches Labor Wien / Forensic Toxicological Center (FTC) Vienna AT Austria (AT)

How to cite

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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