Colamatteo Alessandra, Fusco Clorinda, Matarese Alessandro, Matarese Giuseppe
1Treg Cell Lab, Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università degli Studi di Napoli "Federico II," Napoli, Italy; email:
2Dipartimento di Medicina Clinica e Chirurgia, Università degli Studi di Napoli "Federico II," Napoli, Italy.
Annu Rev Nutr. 2025 May 5. doi: 10.1146/annurev-nutr-111324-122456.
The relationship between obesity and autoimmune diseases has attracted significant attention in recent years, highlighting the multifaceted connection between metabolic dysregulation and loss of self-immune tolerance. Compelling epidemiological evidence has revealed an elevated prevalence of autoimmune diseases among overweight or obese individuals, suggesting a potential causal link. Mechanistically, adipose tissue is a key immunometabolic organ that secretes an array of adipocytokines that can facilitate proinflammatory immune responses against selfantigens. Indeed, adipose tissue dysfunction in obesity fosters a state of chronic low-grade inflammation, which may contribute to the so-called accelerator hypothesis, in which circulating self-autoreactive T cells can easily lose their regulatory mechanisms, resulting in self-tissue damage and autoinflammation. In this review, we elucidate the intricate immunometabolic pathomechanisms underlying the obesity and autoimmunity epidemic, and we explore innovative therapeutic avenues that could be pivotal for advancing public health initiatives in the context of this epidemic.
近年来,肥胖与自身免疫性疾病之间的关系已引起广泛关注,凸显了代谢失调与自身免疫耐受丧失之间的多方面联系。有力的流行病学证据显示,超重或肥胖个体中自身免疫性疾病的患病率有所上升,提示可能存在因果关系。从机制上讲,脂肪组织是关键的免疫代谢器官,可分泌一系列脂肪细胞因子,这些因子能够促进针对自身抗原的促炎免疫反应。实际上,肥胖中的脂肪组织功能障碍会引发慢性低度炎症状态,这可能有助于所谓的加速假说,即循环中的自身反应性T细胞容易失去其调节机制,导致自身组织损伤和自身炎症。在本综述中,我们阐明了肥胖与自身免疫性疾病流行背后复杂的免疫代谢发病机制,并探索了创新的治疗途径,这些途径对于推进针对该流行情况的公共卫生举措可能至关重要。