Inflammatory memory: the core mechanism driving allergic asthma recurrence and chronicity

Advances in biomarker discovery, inhalation therapy, biologics, and bronchial thermoplasty have significantly improved the clinical prognosis and symptom control in patients with asthma. However, recurrence and chronicity of the disease after treatment withdrawal is still a core challenge in clinical management. The emerging concept of inflammatory memory has provided a new perspective for understanding the recurrent remission-relapse cycle in asthma. During asthma onset and development, immune cells and airway structural cells acquire persistent pathogenic memory traits through epigenetic and metabolic reprogramming, thereby amplifying the efficacy of allergen recognition and presentation resulting in local memory niches. These reduce the threshold for airway responses and mediate irreversible airway structural remodeling. In addition, infection, as a key environmental factor, modulates both asthma susceptibility and severity through cross-antigen activation, immune skewing and epigenetic training. Evidence from animal studies suggests that current therapies (especially biological agents) may have the potential to modulate long-resident pathogenic memory immune cells by targeting key cells and inflammatory pathways. However, there are still clinical challenges in the application from animal models to asthma patients. Future interventions should focus on targeting the formation, maintenance, and reactivation of inflammatory memory to attenuate the potential pathogenic memory program in asthma. In this review, we systematically discuss the multi-layered mechanisms of inflammatory memory in asthma pathogenesis, emphasizing the importance of exploring novel strategies for inflammatory memory intervention toward achieving long-term remission.