CD14+ monocytes are vulnerable and functionally impaired under endoplasmic reticulum stress in patients with type 2 diabetes.
CD14+ monocytes are vulnerable and functionally impaired under endoplasmic reticulum stress in patients with type 2 diabetes.
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作者：
Komura T;Sakai Y;Honda M;Takamura T;Matsushima K;Kaneko S
虽然糖尿病患者由于免疫功能受损而遭受感染增加和癌症发病率较高，但缺乏关于糖尿病引起的免疫力下降的细节。我们评估了免疫介导的外周血单核细胞（PBMC）在糖尿病中的作用。从33例2型糖尿病患者和28名健康志愿者中，我们获得了PBMC，并研究了其对凋亡和功能改变的易感性。在PBMC亚群中，来自糖尿病患者的单核细胞比来自健康志愿者的单核细胞更容易凋亡。糖尿病患者的单核细胞吞噬活性降低，对Toll样受体（TLR）配体的反应较低，尽管两组之间TLR的表达没有显著差异。此外，从糖尿病患者的单核细胞有一个明显不同的基因表达谱相比，从正常志愿者单核细胞的DNA微阵列分析评估。具体而言，定量实时检测PCR测量显示糖尿病单核细胞中内质网（ER）应激标志物的表达升高，单核细胞的电子显微镜检查显示糖尿病患者来源的细胞ER的形态学改变。因此，ER应激诱导剂衣霉素增加了健康单核细胞的凋亡，并减弱了对TLR配体的促炎反应。这些数据表明，单核细胞构成了糖尿病患者PBMC的一个基本受损的亚群，ER应激机制上参与了这些病理变化。这意味着受影响的单核细胞应进一步研究，以更好地了解糖尿病免疫。
Although patients with diabetes suffer from increased infections and a higher incidence of cancer due to impaired immune function, details on diabetes-induced decrease in immunity are lacking. We assessed how immune-mediating peripheral blood mononuclear cells (PBMCs) are affected in diabetes. From 33 patients with type 2 diabetes and 28 healthy volunteers, we obtained PBMCs and investigated their susceptibility to apoptosis and functional alteration. In a subpopulation of PBMCs, monocytes derived from patients with diabetes were more susceptible to apoptosis than monocytes from healthy volunteers. Monocytes from patients with diabetes had decreased phagocytotic activity and were less responsive to Toll-like receptor (TLR) ligands, although the expression of TLRs did not differ significantly between the two groups. Furthermore, monocytes from patients with diabetes had a distinctly different gene expression profile compared with monocytes from normal volunteers as assessed with DNA microarray analysis. Specifically, quantitative real-time detection PCR measurements showed an elevated expression of the markers of endoplasmic reticulum (ER) stress in diabetic monocytes, and electron microscopic examination of monocytes revealed morphologic alterations in the ER of cells derived from patients with diabetes. Consistently, the ER stress inducer tunicamycin increased apoptosis of otherwise healthy monocytes and attenuated the proinflammatory responses to TLR ligands. These data suggest that monocytes comprise a substantially impaired subpopulation of PBMCs in patients with diabetes and that ER stress is involved in these pathologic changes mechanistically. This implies that the affected monocytes should be investigated further to better understand diabetic immunity.
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