Programmed cell death in allergic rhinitis: pathogenic mechanisms and therapeutic potential from a cellular perspective

Allergic rhinitis (AR), a prevalent chronic inflammatory respiratory disease, is increasing in global incidence, significantly compromising patients' quality of life and imposing considerable socioeconomic burdens. Given the limitations of current clinical treatments, elucidating the pathogenesis of AR is critical for advancing precision therapeutics. Programmed cell death (PCD), which encompasses apoptosis, autophagy, pyroptosis, and other forms, plays a pivotal role in AR. Emerging evidence indicates that dysregulated PCD is closely linked to aberrant immune cell states, such as epithelial cells, dendritic cells, eosinophils, and T-cell subsets, in the nasal mucosa of AR patients. Such dysregulation disrupts nasal mucosal epithelial barrier integrity, impairs immune cell function, and promotes inflammatory cytokine dysregulation. Although PCD-targeted therapies have shown promise in preclinical and clinical studies, significant challenges remain. This review systematically demonstrates the close relationship between the damage of nasal mucosal epithelial cells and the imbalance of immune cell subsets in the pathogenesis of AR, revealing that its essence lies in the imbalance of the homeostasis of the immune microenvironment and the regulatory network of cell death. By constructing a cellular-level dynamic PCD regulatory map, we explore the molecular mechanisms underlying diverse PCD forms in AR progression and propose targeted intervention strategies. Our findings aim to provide a novel theoretical framework and therapeutic avenues for precision AR treatment.