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Adiponectin receptors sustain haematopoietic stem cells throughout adulthood by protecting them from inflammation
Nature Cell Biology ( IF 17.3 ) Pub Date : 2022-05-05 , DOI: 10.1038/s41556-022-00909-9
Corbin E Meacham 1 , Elise C Jeffery 1 , Rebecca J Burgess 1 , Charukesi D Sivakumar 1 , Madison A Arora 1 , Anne Marie Stanley 1 , Emily M Colby 1 , Genevieve M Crane 2 , Zhiyu Zhao 1 , Sean J Morrison 1, 3
Affiliation  

How are haematopoietic stem cells (HSCs) protected from inflammation, which increases with age and can deplete HSCs? Adiponectin, an anti-inflammatory factor that is not required for HSC function or haematopoiesis, promotes stem/progenitor cell proliferation after bacterial infection and myeloablation. Adiponectin binds two receptors, AdipoR1 and AdipoR2, which have ceramidase activity that increases upon adiponectin binding. Here we found that adiponectin receptors are non-cell-autonomously required in haematopoietic cells to promote HSC quiescence and self-renewal. Adiponectin receptor signalling suppresses inflammatory cytokine expression by myeloid cells and T cells, including interferon-γ and tumour necrosis factor. Without adiponectin receptors, the levels of these factors increase, chronically activating HSCs, reducing their self-renewal potential and depleting them during ageing. Pathogen infection accelerates this loss of HSC self-renewal potential. Blocking interferon-γ or tumour necrosis factor signalling partially rescues these effects. Adiponectin receptors are thus required in immune cells to sustain HSC quiescence and to prevent premature HSC depletion by reducing inflammation.



中文翻译:


脂联素受体通过保护造血干细胞免受炎症影响来维持其整个成年期



如何保护造血干细胞 (HSC) 免受炎症的影响?炎症会随着年龄的增长而增加,并会耗尽 HSC 细胞?脂联素是一种 HSC 功能或造血不需要的抗炎因子,可在细菌感染和清髓后促进干细胞/祖细胞增殖。脂联素结合两种受体,AdipoR1 和 AdipoR2,其神经酰胺酶活性在脂联素结合后增加。在这里,我们发现脂联素受体是造血细胞非细胞自主地需要的,以促进HSC静止和自我更新。脂联素受体信号传导抑制骨髓细胞和 T 细胞的炎性细胞因子表达,包括干扰素-γ 和肿瘤坏死因子。如果没有脂联素受体,这些因子的水平就会增加,从而长期激活造血干细胞,降低其自我更新潜力,并在衰老过程中耗尽它们。病原体感染会加速 HSC 自我更新潜力的丧失。阻断干扰素-γ或肿瘤坏死因子信号传导可以部分挽救这些效应。因此,免疫细胞需要脂联素受体来维持 HSC 静止并通过减少炎症来防止 HSC 过早耗尽。

更新日期:2022-05-09
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