Details

Autor(en) / Beteiligte

• Luo, Bangwei
• Gan, Woting
• Liu, Zongwei
• Shen, Zigang
• Wang, Jinsong
• Shi, Rongchen
• Liu, Yuqi
• Liu, Yu
• Jiang, Man
• Zhang, Zhiren
• Wu, Yuzhang

Titel

Erythropoeitin Signaling in Macrophages Promotes Dying Cell Clearance and Immune Tolerance

Ist Teil von

• Immunity (Cambridge, Mass.), 2016-02, Vol.44 (2), p.287-302

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2016

Quelle

MEDLINE

Beschreibungen/Notizen

• The failure of apoptotic cell clearance is linked to autoimmune diseases, nonresolving inflammation, and developmental abnormalities; however, pathways that regulate phagocytes for efficient apoptotic cell clearance remain poorly known. Apoptotic cells release find-me signals to recruit phagocytes to initiate their clearance. Here we found that find-me signal sphingosine 1-phosphate (S1P) activated macrophage erythropoietin (EPO) signaling promoted apoptotic cell clearance and immune tolerance. Dying cell-released S1P activated macrophage EPO signaling. Erythropoietin receptor (EPOR)-deficient macrophages exhibited impaired apoptotic cell phagocytosis. EPO enhanced apoptotic cell clearance through peroxisome proliferator activated receptor-γ (PPARγ). Moreover, macrophage-specific Epor−/− mice developed lupus-like symptoms, and interference in EPO signaling ameliorated the disease progression in lupus-like mice. Thus, we have identified a pathway that regulates macrophages to clear dying cells, uncovered the priming function of find-me signal S1P, and found a role of the erythropoiesis regulator EPO in apoptotic cell disposal, with implications for harnessing dying cell clearance. [Display omitted] •Dying cell-released S1P activates macrophage EPO signaling in vitro and in vivo•Macrophage EPO signaling is central for the immunosilent disposal of dying cells•EPO enhances dying cell clearance through upregulating PPARγ in macrophages•Macrophage-specific Epor−/− mice develope age-dependent lupus-like symptoms The efficient apoptotic cell clearance is essential for immune tolerance. However, pathways that regulate phagocytes for timely dying cell clearance before engulfment remain poorly known. Zhang and colleagues identify that “find-me” signal sphingosine 1-phosphate activated macrophage erythropoietin signaling promotes dying cell clearance and immune tolerance.