GM-CSF impairs erythropoiesis by disrupting erythroblastic island formation via macrophages.
GM-CSF impairs erythropoiesis by disrupting erythroblastic island formation via macrophages.
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DOI：
10.1186/s12967-021-03214-5
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发表时间：
2022-01-03
影响因子：
7.4
通讯作者：
Jiang Z
中科院分区：
文献类型：
--
作者：
Cao W;Fan W;Wang F;Zhang Y;Wu G;Shi X;Shi JX;Gao F;Yan M;Guo R;Li Y;Li W;Du C;Jiang Z
贫血是慢性炎症的一个重要并发症，可能与红细胞岛（EBI）巨噬细胞的活动失调有关。据报道，GM-CSF 被上调，并被作为许多炎症性疾病的治疗靶点。在EBI中，我们发现GM-CSF受体在EBI巨噬细胞中优先且高度表达，但在成红细胞中不表达。 GM-CSF 治疗通过降低 CD163 粘附分子的表达，显着减少体外人类 EBI 的形成。 RNA 序列分析表明，GM-CSF 治疗会损害人 EBI 巨噬细胞在红细胞生成过程中的支持功能。 GM-CSF 治疗还将人类 EBI 巨噬细胞从 M2 样类型极化为 M1 样类型。此外，GM-CSF 还能减少小鼠骨髓 (BM) 成红细胞和 EBI 巨噬细胞，从而导致 EBI 数量减少。在定义工作的分子机制时，我们发现 GM-CSF 治疗显着降低了体内 CD163 和 Vcam1 的粘附分子表达。重要的是，GM-CSF 治疗还降低了小鼠 BM 中 EBI 巨噬细胞的吞噬率，并降低了吞噬相关分子 Mertk、Axl 和 Timd4 的表达。此外，GM-CSF治疗使小鼠BM EBI巨噬细胞从M2样类型极化为M1样类型。因此，我们证明 GM-CSF 会损害小鼠和人类的 EBI 形成。我们的研究结果表明，靶向 GM-CSF 或重编程 EBI 巨噬细胞可能是治疗炎症性疾病引起的贫血的新策略。在线版本包含可在 10.1186/s12967-021-03214-5 获取的补充材料。
Anemia is a significant complication of chronic inflammation and may be related to dysregulated activities among erythroblastic island (EBI) macrophages. GM-CSF was reported to be upregulated and attracted as a therapeutic target in many inflammatory diseases. Among EBIs, we found that the GM-CSF receptor is preferentially and highly expressed among EBI macrophages but not among erythroblasts. GM-CSF treatment significantly decreases human EBI formation in vitro by decreasing the adhesion molecule expression of CD163. RNA-sequence analysis suggests that GM-CSF treatment impairs the supporting function of human EBI macrophages during erythropoiesis. GM-CSF treatment also polarizes human EBI macrophages from M2-like type to M1-like type. In addition, GM-CSF decreases mouse bone marrow (BM) erythroblasts as well as EBI macrophages, leading to a reduction in EBI numbers. In defining the molecular mechanism at work, we found that GM-CSF treatment significantly decreases the adhesion molecule expression of CD163 and Vcam1 in vivo. Importantly, GM-CSF treatment also decreases the phagocytosis rate of EBI macrophages in mouse BM as well as decreases the expression of the engulfment-related molecules Mertk, Axl, and Timd4. In addition, GM-CSF treatment polarizes mouse BM EBI macrophages from M2-like type to M1-like type. Thus, we document that GM-CSF impairs EBI formation in mice and humans. Our findings support that targeting GM-CSF or reprogramming EBI macrophages might be a novel strategy to treat anemia resulting from inflammatory diseases. The online version contains supplementary material available at 10.1186/s12967-021-03214-5.
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影响因子：
2.3
作者：
Ikuta, Tohru;Adekile, Adekunle D.;Head, C. Alvin
通讯作者：
Head, C. Alvin
影响因子：
10.1
作者：
Heideveld E;Hampton-O'Neil LA;Cross SJ;van Alphen FPJ;van den Biggelaar M;Toye AM;van den Akker E
通讯作者：
van den Akker E
影响因子：
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影响因子：
100.3
作者：
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通讯作者：
Hamilton, John A.
影响因子：
20.3
作者：
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通讯作者：
Paulson, Robert F.