Recent updates on thymic stromal lymphopoietin as a therapeutic target for asthma

Thymic stromal lymphopoietin (TSLP) is an epithelial-derived cytokine shown to bridge innate and adaptive immunity, and orchestrates airway inflammation across both type 2 (T2)-high and T2-low asthma. Emerging evidence suggests that by functioning as an alarmin upstream of airway immune cells, TSLP integrates epithelial and immune signaling to initiate inflammation and structural remodeling, positioning it as a pivotal therapeutic target in asthma pathogenesis.

This review summarizes the current understanding of TSLP biology and its roles in both T2- high and T2-low inflammation. Clinical data from tezepelumab treatment and emerging next-generation anti-TSLP agents, including bispecific antibodies, receptor antagonists and inhaled formulation, are evaluated for their potential to transform asthma management.

Targeting TSLP represents a paradigm shift in asthma therapy, offering efficacy across diverse inflammatory endotypes, however with greater benefit in T2-high patients. Next-generation anti-TSLP agents aim to enhance potency, durability and tissue specificity, and combine with other agents for bi-specific therapy. Despite this progress in clinical development, key challenges remain, including understanding isoform-specific functions, improving biomarker-based patient stratification and assessing long-term safety of TSLP inhibition. As research advances, TSLP inhibition is expected to evolve from the strategy of single cytokine blockade into a personalized multi-pathway approach.