Dept. Environmental Medicine, Poznan University of Medical Sciences, Fredry 10, 61-701 Poznan, Poland, Dept. Gastroenterology, Dietetics and Internal Diseases, Poznan University of Medical Sciences, Fredry 10, 61-701 Poznan, Poland.
Institute of Human Genetics, Polish Academy of Science, Strzeszynska 32, 60-479 Poznan, Poland.
Eur Cytokine Netw. 2021 Dec 1;32(4):64-72. doi: 10.1684/ecn.2021.0474.
The abnormal accumulation of visceral adipose tissue in obesity is associated with metabolic changes that include altered glucose tolerance, insulin resistance, hyperlipidemia, and metabolic syndrome. Obesity also coincides with increased incidence of autoimmune diseases. Accumulating evidence suggest that prolonged metabolic overload related to overnutrition, influenced by genetic and epigenetic factors, might affect immunologic self-tolerance through changes in the energy metabolism of immune cells, particularly regulatory T (Treg) cells. A strong activation of nutrient-energy signaling pathways blocks the induction of the transcription factor forkhead P3 (FOXP3), a master regulator of Treg cells, consequently inhibiting their generation and proliferation, thereby promoting proinflammatory response. Expanding our knowledge on the topic, particularly on metabolic T cell flexibility in vivo will provide new insights that can be used to develop therapeutic strategies for various inflammatory diseases, including obesity and autoimmune diseases. Targeting specific metabolic pathways is emerging as an important approach to control immune response and maintain immunological homeostasis.
肥胖症患者内脏脂肪组织异常堆积与代谢变化相关,包括葡萄糖耐量异常、胰岛素抵抗、血脂异常和代谢综合征。肥胖症还伴随着自身免疫性疾病发病率的增加。越来越多的证据表明,与营养过剩相关的长期代谢超负荷,受遗传和表观遗传因素的影响,可能通过改变免疫细胞的能量代谢,特别是调节性 T(Treg)细胞,影响免疫耐受自我。营养-能量信号通路的强烈激活会阻止转录因子叉头 P3(FOXP3)的诱导,FOXP3 是 Treg 细胞的主要调节因子,从而抑制其生成和增殖,从而促进促炎反应。深入了解这一课题,特别是在体内代谢 T 细胞灵活性方面的知识,将为开发针对各种炎症性疾病(包括肥胖症和自身免疫性疾病)的治疗策略提供新的见解。靶向特定的代谢途径正成为控制免疫反应和维持免疫稳态的重要方法。