Macrophage autophagy in allergic diseases: Regulatory mechanisms, immune crosstalk, and therapeutic implications.

Abstract

Macrophages are pivotal effector cells within the innate immune system, playing a central role in inflammation regulation, tissue homeostasis, and immune defense. Recent studies have demonstrated that macrophage autophagy-a highly conserved process essential for cellular homeostasis-plays a critical role in dynamically balancing immune responses by selectively eliminating damaged organelles, pathogens, and protein aggregates. Macrophage autophagy is finely regulated by various signaling pathways, such as mTOR and NF-κB, and its dysfunction is closely associated with the onset and progression of allergic diseases. This review systematically synthesizes the molecular mechanisms governing macrophage autophagy and its dual role in allergic diseases, including allergic rhinitis, asthma, and atopic dermatitis. It highlights the functions of key signaling pathways (e.g., mTOR, NF-κB) and regulatory factors (e.g., p62, Beclin-1, LC3) and explores the crosstalk between macrophage autophagy, immunometabolism, and cellular polarization. Explores the crosstalk between macrophage autophagy, immunometabolism, and cellular polarization, and further elaborates the reciprocal regulatory network of autophagy and metabolic reprogramming within allergic inflammatory microenvironment. Furthermore, the review summarizes potential therapeutic strategies targeting macrophage autophagy, such as budesonide/simvastatin combination therapy and rapamycin derivatives, along with their clinical translation prospects, with the aim of providing a theoretical foundation for developing novel, autophagy-targeted precision therapies for allergic diseases.