2型糖尿病患者的血液特征及其外周血单个核细胞对nlrp3炎性体和caspase-1抑制剂的反应

IF 2.6
Joyce de Paula Souza, Justus S Fischer, Karine Jeanneau, Cyril Allard, Eline Angevaare, Dominik Aschenbrenner, Ursula Bodendorf, Benjamin Demarco, John S Gounarides, Saskia Killmer, Jiri Kovarik, Sabina Pfister, Hong Yin, Vithushan Ratnarasa, Marianne Bo Ni-Schnetzler, Matthias Hepprich, Daniel T Meier, Grazyna Wieczorek, Marc Y Donath
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引用次数: 0

摘要

肥胖和衰老与先天免疫系统活动的增加有关。这种慢性全身性炎症有助于2型糖尿病和长期并发症的发展,部分是由NLRP3炎症小体的激活驱动的。我们对健康个体和2型糖尿病患者的临床参数、非酯化脂肪酸(NEFA)谱、免疫细胞亚群和外周血单个核细胞的炎症反应进行了比较分析。血浆NEFA分析显示,2型糖尿病患者的NEFA失调,表明血脂、白细胞增多、血清炎症细胞因子、炎性小体相关蛋白ASC、IL-1RA和IL-18BPa水平升高可能调节免疫细胞反应。令人惊讶的是,功能评估显示两组外周血单核细胞(PBMCs)中NLRP3炎性体活性相当,这表明2型糖尿病的全身性炎症是由白细胞数量升高或驻留组织巨噬细胞驱动的。用NLRP3和caspase-1抑制剂治疗pbmc可减少促炎细胞因子的体外释放。因此,抑制炎性体的激活成为治疗糖尿病相关并发症的一种很有前景的治疗策略。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Blood characteristics of patients with type 2 diabetes and response of their peripheral blood mononuclear cells to inhibitors of the NLRP3-inflammasome and caspase-1.

Obesity and aging are associated with increased activity of the innate immune system. This chronic systemic inflammation contributes to the development of type 2 diabetes and long-term complications and is partly driven by the activation of the NLRP3 inflammasome. We conducted a comparative analysis of clinical parameters, non-esterified fatty acid (NEFA) profiles, immune cell subsets, and inflammatory responses of peripheral blood mononuclear cells obtained from both healthy individuals and those diagnosed with type 2 diabetes. Plasma NEFA profiling revealed a dysregulation in patients with type 2 diabetes, indicating potential modulation of immune cell responses by lipids, along with leukocytosis, elevated serum levels of inflammatory cytokines, the inflammasome-related protein ASC, IL-1RA, and IL-18BPa. Surprisingly, functional assessments demonstrated comparable NLRP3 inflammasome activity in peripheral blood mononuclear cells (PBMCs) from both groups, suggesting that systemic inflammation in type 2 diabetes is driven by elevated leucocyte numbers or resident tissue macrophages. Treatment of PBMCs with NLRP3 and caspase-1 inhibitors attenuated the release of pro-inflammatory cytokines ex vivo. Therefore, inhibition of inflammasome activation emerges as a promising therapeutic strategy for management of diabetes-related complications.

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