Summary:
This article examines how diet influences the immune system and the development of autoimmune diseases, with a particular focus on a cellular process called autophagy. Autophagy is a normal recycling system in cells that removes damaged components and helps maintain immune balance. The authors explain that this process links what we eat to how the immune system behaves, and may help explain why certain diets increase or reduce the risk of chronic inflammatory and autoimmune conditions. Both nutrient deficiencies (such as low levels of vitamin D, zinc, selenium, and omega-3 fatty acids) and poor nutrition can disrupt immune regulation. Poor nutrition is linked with increased inflammation, changes in gut bacteria, and weakened barriers in the gut, all of which can contribute to immune dysfunction. These changes can increase the risk of persistent inflammation and autoimmune diseases such as rheumatoid arthritis, multiple sclerosis, and inflammatory bowel disease. A key focus of this paper is how diet affects autophagy, as certain dietary patterns, such as fasting or calorie restriction, may activate autophagy by switching on energy systems in cells. In contrast, high-sugar and high-fat diets may suppress autophagy and increase cellular stress. When autophagy is not working properly, immune cells may fail to clear damaged material, which can lead to inappropriate immune activation and autoimmunity. The paper also highlights that genetic differences in autophagy-related genes can make some people more susceptible to autoimmune diseases. In these individuals, environmental factors such as diet may have a stronger effect on disease risk. This suggests that both genetics and nutrition work together to influence immune health through autophagy pathways. Overall, this is a narrative review that brings together existing research to explain how diet, autophagy, and immune function are connected. The authors conclude that targeting autophagy through diet may be a future strategy for preventing or managing autoimmune diseases.
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Abstract:
Autophagy is a highly conserved lysosomal recycling pathway that couples nutrient availability to cellular quality control and immune regulation. Accumulating evidence identifies autophagy as a central mechanistic interface through which dietary exposures influence metabolic inflammation and the maintenance or breakdown of immune tolerance in autoimmune diseases. This review synthesizes current molecular and cellular insights into how nutrition modulates autoimmune susceptibility and disease activity by shaping autophagic pathways across immune and metabolic tissues. Dietary signals exert bidirectional and context-dependent effects on immune homeostasis. Deficiencies in key micronutrients, including vitamin D, zinc, selenium, and omega-3 fatty acids, can impair regulatory immune circuits and promote pro-inflammatory cytokine profiles. Conversely, overnutrition, obesity, and Westernized dietary patterns drive chronic low-grade inflammation, compromise epithelial barrier integrity, and remodel the gut microbiota, thereby amplifying systemic immune activation and autoantibody-related pathways. The review describes major autophagy programs and highlights their roles in lymphocyte survival and memory, antigen presentation, and cytokine regulation. Genetic and experimental evidences indicate that defective autophagy and lysosomal dysfunction can alter antigen handling and perpetuate pathological immune activation. Nutritional regulation of autophagy is discussed through nutrient-sensing pathways, particularly mechanistic target of rapamycin complex 1, AMP-activated protein kinase, and sirtuin 1. Fasting-based strategies and time-restricted eating may enhance autophagic competence, whereas high-glycemic, obesogenic diets can suppress autophagy and intensify oxidative and endoplasmic reticulum stress. Finally, a precision immunonutrition framework is proposed that integrates genetic susceptibility, microbiota features, metabolic profiling, and autophagy biomarkers to guide individualized, adjunctive interventions in autoimmune diseases.
Article Publication Date: 01/04/2026
DOI: 10.1016/j.autrev.2026.104040
