Anti-TSLP Monoclonal Antibody (Tezepelumab)

Thymic stromal lymphopoietin (TSLP) is an epithelial cell-derived type 2 cytokine belonging to the IL-2 family, characterized by a unique four-helix bundle structure that activates downstream JAK-STAT signaling through binding to a heterodimeric receptor complex composed of TSLP receptor (TSLPR) and IL-7Rα. As an "alarmin," TSLP plays a pivotal role in initiating airway inflammation: upon stimulation by allergens, viruses, or pollutants, epithelial cells rapidly release TSLP, which directly acts on dendritic cells to promote Th2 cell differentiation while simultaneously activating mast cells, eosinophils, and type 2 innate lymphoid cells (ILC2), driving the production of inflammatory mediators such as IL-4, IL-5, and IL-13 to establish type 2-high inflammatory responses; additionally, TSLP can enhance airway hyperresponsiveness and remodeling through non-type 2 pathways. The anti-TSLP monoclonal antibody tezepelumab blocks the interaction between TSLP and its receptors, thereby suppressing inflammatory cascades at their source. Its clinical significance lies in overcoming the limitations of conventional biologics that target only single inflammatory pathways, establishing itself as the first broad-spectrum biologic therapy effective in patients with both normal eosinophil counts and non-type 2 asthma, thereby offering a novel precision treatment option for severe uncontrolled asthma.