CD169-CD43 interaction is involved in erythroblastic island formation and erythroid differentiation.
CD169-CD43 interaction is involved in erythroblastic island formation and erythroid differentiation.
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DOI：
10.3324/haematol.2022.282192
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发表时间：
2023-08-01
期刊：
影响因子：
10.1
通讯作者：
Qin, Hongyan
中科院分区：
文献类型：
--
作者：
Bai, Jian;Fan, Fan;Gao, Chunchen;Li, Shaohua;Li, Wei;Wei, Tiaoxia;Cheng, Shilin;Yu, Jinmin;Zheng, Chao;Zhao, Junlong;Zou, Linru;Feng, Lei;Yi, Jing;Qin, Hongyan
CD169是巨噬细胞的特异性标志物，是唾液酸结合免疫球蛋白样凝集素（Siglec）家族的成员，通过唾液化糖缀合物作为粘附分子参与细胞-细胞相互作用。虽然CD169+巨噬细胞已被发现参与红母细胞岛（EBI）的形成并在稳态和应激下支持红细胞生成，但CD169及其对抗受体在EBI中的确切作用尚不清楚。在此，我们构建了CD169- creert敲入小鼠，并使用CD169缺失小鼠研究了CD169在EBI形成和红细胞生成中的功能。使用抗CD169抗体阻断CD169和巨噬细胞上的CD169缺失均可破坏体外EBI的形成。此外，通过表面等离子体共振和成像流式细胞术，发现早期红细胞（EB）表达的CD43是CD169介导EBI形成的对抗受体。有趣的是，CD43被证明是红细胞分化的新指标，因为随着EB成熟，CD43的表达会逐渐减少。虽然CD169缺失的小鼠在体内没有表现出骨髓EBI形成缺陷，但CD169缺失可能会在应激红细胞生成下通过CD43阻碍骨髓红细胞分化，这与CD169重组蛋白在血红素诱导的K562红细胞分化中的作用一致。这些发现揭示了CD169通过与其对抗受体CD43结合在稳定和应激性红细胞生成中在EBI中的作用，提示CD169-CD43相互作用可能是红细胞疾病的一个有希望的治疗靶点。
CD169, a specific marker for macrophages, is a member of the sialic acid-binding immunoglobulin-like lectin (Siglec) family which acts as an adhesion molecule implicated in cell–cell interaction via sialylated glycoconjugates. Although CD169+ macrophages have been found to participate in erythroblastic island (EBI) formation and support erythropoiesis under homeostasis and stress, the exact role of CD169 and its counter receptor in EBI remains unknown. Herein, we generated CD169-CreERT knock-in mice and investigated the function of CD169 in EBI formation and erythropoiesis using CD169-null mice. EBI formation was impaired in vitro by both blockade of CD169 using anti-CD169 antibody and deletion of CD169 on macrophages. Furthermore, CD43 expressed by early erythroblasts (EB) was identified as the counter receptor for CD169 in mediating the EBI formation via surface plasmon resonance and imaging flow cytometry. Interestingly, CD43 was proven to be a novel indicator of erythroid differentiation due to the progressive decrease of CD43 expression as EB mature. Although CD169-null mice did not display defects in bone marrow (BM) EBI formation in vivo, CD169 deficiency impeded BM erythroid differentiation probably via CD43 under stress erythropoiesis, in concert with the role of CD169 recombinant protein in hemin-induced K562 erythroid differentiation. These findings have shed light on the role of CD169 in EBI under steady and stress erythropoiesis through binding with its counter receptor CD43, suggesting that CD169-CD43 interaction might be a promising therapeutic target for erythroid disorders.
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影响因子：
64.5
作者：
Haldar M;Kohyama M;So AY;Kc W;Wu X;Briseño CG;Satpathy AT;Kretzer NM;Arase H;Rajasekaran NS;Wang L;Egawa T;Igarashi K;Baltimore D;Murphy TL;Murphy KM
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影响因子：
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影响因子：
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Jiang Z