Autoimmunity, diet and autophagy

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.