Interleukin-23 in lung and airway diseases: from pathogenesis to precision-guided therapeutic targeting

Interleukin-23 (IL-23) is a pleiotropic cytokine belonging to the IL-12 family and is predominantly produced by antigen-presenting cells. It plays a central role in shaping adaptive immunity by promoting the polarization, expansion, and maintenance of T helper 17 (Th17) cells, thereby driving the production of downstream effector cytokines such as IL-17A and IL-22. Under physiological conditions, IL-23 contributes to pulmonary immune homeostasis and host defense against bacterial and fungal pathogens. However, sustained or dysregulated IL-23 signaling promotes chronic inflammation and tissue damage. Beyond autoimmune diseases, where IL-23 is a well-established key mediator linked to disease severity and a validated therapeutic target, it has also emerged as a critical mediator in chronic lung diseases. Enhanced IL-23 signaling has been associated with increased disease severity, corticosteroid resistance, airway remodeling, and progressive tissue fibrosis, highlighting its contribution to both inflammatory and structural components of lung pathology. These findings suggest that IL-23 is not merely a bystander but an active driver of pathogenic processes in the respiratory system. In this review, we synthesize recent advances in understanding the role of IL-23 in chronic obstructive pulmonary disease, asthma, idiopathic pulmonary fibrosis, and coronavirus disease 2019. We further discuss the therapeutic potential of targeting IL-23 as a precision-guided strategy to modulate respiratory inflammation and remodeling, with particular emphasis on corticosteroid resistance, fibrotic endotypes, safety and pharmacologic tradeoffs, and the emerging role of IL-23-related biomarkers and molecular endotyping for precision-guided patient stratification and targeted intervention.