Diabetes induces dysregulation throughout the spectrum of myeloid lineage cells from progenitors to terminally differentiated cells. Another complication of diabetes is persistent inflammation, including prolonged accumulation of macrophages, which contributes to impaired wound healing. However, it remains unclear whether diabetes disrupts the response of bone marrow progenitors to peripheral injury and whether such dysregulation leads to sustained inflammation and impaired healing. Here, we demonstrated that diabetic mice (db/db, referred to here as DB) exhibit myeloid lineage bias during homeostasis and following injury. In addition, cells in the LSK (Lin- Sca-1+ cKit+ ) population of DB mice are preprogrammed towards myeloid commitment at the transcriptional level, and cultured myeloid progenitors from DB mice produce more monocytes ex vivo than their non-diabetic counterparts. We also show via bone marrow transfer between interleukin-1 receptor 1 KO (Il1r1-/- ) and DB mice that IL-1R1 signaling is likely not involved in myeloid skewing in DB mice. Furthermore, in vitro experiments indicated that macrophage colony-stimulating factor receptor signaling is not likely involved in enhanced myeloid transcription factor expression in LSK cells of DB mice. Our findings indicate that myeloid lineage commitment in bone marrow may contribute to increased macrophage numbers observed in diabetic skin wounds, and that strategies to regulate monopoiesis during homeostasis or post-wounding may improve diabetic wound healing. © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

中文翻译：

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糖尿病在骨髓祖细胞中引起髓样偏见，与伤口巨噬细胞积累增强和愈合受损有关。

从祖细胞到终末分化的细胞，糖尿病都在整个髓系谱系细胞中引起失调。糖尿病的另一种并发症是持续性炎症，包括巨噬细胞的长期积累，这会损害伤口的愈合。但是，尚不清楚糖尿病是否会破坏骨髓祖细胞对周围损伤的反应，以及这种失调是否会导致持续的炎症和损害的康复。在这里，我们证明了糖尿病小鼠（db / db，在此称为DB）在体内平衡过程中和受伤后均表现出髓系谱系偏倚。此外，DB小鼠的LSK（Lin- Sca-1 + cKit +）群体中的细胞已被预先编程为在转录水平上实现骨髓定型，并且来自DB小鼠的培养的髓样祖细胞离体产生的单核细胞要比非糖尿病的同类细胞多。我们还通过白介素1受体1 KO（Il1r1-/-）和DB小鼠之间的骨髓转移显示，IL-1R1信号可能不参与DB小鼠的髓样倾斜。此外，体外实验表明巨噬细胞集落刺激因子受体信号传导可能不参与DB小鼠LSK细胞中增强的髓样转录因子表达。我们的发现表明，骨髓中的骨髓谱系定型可能有助于增加在糖尿病皮肤伤口中观察到的巨噬细胞数量，并且在体内平衡或伤口后调节单生的策略可能会改善糖尿病伤口的愈合。©2019英国和爱尔兰病理学会。由John Wiley＆Sons，Ltd.出版