An essential role of erythropoietin signaling in apoptotic cell clearance and immune tolerance discovered by Yuzhang Wu and Zhiren Zhang Groups
Source：Yuzhang Wu
2016-03-21
Prof. Yuzhang Wu, Zhiren Zhang and colleagues, Institute of Immunology, PLA, Third Military Medical University, have reported that erythropoeitin signaling in macrophages is important for promoting dying cell clearance and immune tolerance. This report entitled “Erythropoeitin signaling in macrophages promotes dying cell clearance and immune tolerance” was published on Immunity.
Apoptosis occurs throughout life in many tissues, and apoptotic cells are efficiently removed in an immunologically silent way by phagocytes to maintain tissue homeostasis. Defective removal of dying cells causes the accumulation and the secondary necrosis of apoptotic cells, which triggers the immune response to self antigens, resulting in a systemic autoimmune disease that resembles human systemic lupus erythematosus (SLE). 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. In this report, the scientists found that find-me signal sphingosine 1-phosphate (S1P) activated macrophage erythropoietin (EPO) signalling to promote apoptotic cell clearance and immune tolerance. They identified that 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, their research 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.
Article： Luo B, Gan W, Liu Z, Shen Z, Wang J, Shi R, Liu Y, Liu Y, Jiang M, Zhang Z*, Wu Y*. Erythropoeitin Signaling in Macrophages Promotes Dying Cell Clearance and Immune Tolerance. Immunity. 2016 Feb 16; 44(2): 287-302. doi:10.1016/j.immuni.2016.01.002. Epub 2016 Feb 9. PubMed PMID: 26872696.
Apoptosis occurs throughout life in many tissues, and apoptotic cells are efficiently removed in an immunologically silent way by phagocytes to maintain tissue homeostasis. Defective removal of dying cells causes the accumulation and the secondary necrosis of apoptotic cells, which triggers the immune response to self antigens, resulting in a systemic autoimmune disease that resembles human systemic lupus erythematosus (SLE). 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. In this report, the scientists found that find-me signal sphingosine 1-phosphate (S1P) activated macrophage erythropoietin (EPO) signalling to promote apoptotic cell clearance and immune tolerance. They identified that 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, their research 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.
Article： Luo B, Gan W, Liu Z, Shen Z, Wang J, Shi R, Liu Y, Liu Y, Jiang M, Zhang Z*, Wu Y*. Erythropoeitin Signaling in Macrophages Promotes Dying Cell Clearance and Immune Tolerance. Immunity. 2016 Feb 16; 44(2): 287-302. doi:10.1016/j.immuni.2016.01.002. Epub 2016 Feb 9. PubMed PMID: 26872696.
