Thymic stromal lymphopoietin (TSLP) is an epithelial cell-derived cytokine belonging to the IL-2 family, initially identified as a growth factor for B cells. Subsequent studies revealed its critical role in bridging innate and adaptive immune responses, particularly in driving type 2 inflammation. TSLP activates dendritic cells, mast cells, and T-helper 2 (Th2) cells, promoting the release of pro-inflammatory cytokines like IL-4. IL-5. and IL-13. This pathway is strongly implicated in allergic diseases such as asthma, atopic dermatitis, and chronic rhinosinusitis, where epithelial barrier dysfunction and environmental triggers (e.g., allergens, pollutants) induce TSLP overexpression.
Given its central role in type 2 inflammation, TSLP became a therapeutic target. TSLP-blocking antibodies, like tezepelumab, bind to TSLP to prevent its interaction with the TSLP receptor complex (TSLPR/IL-7Rα). Clinical trials demonstrated efficacy in reducing exacerbations and improving lung function in severe asthma, regardless of eosinophil levels, leading to FDA approval in 2021. Research also explores their potential in other TSLP-mediated conditions, including eczema and food allergies.
TSLP inhibitors represent a breakthrough in precision medicine for allergic diseases, offering broader targeting of multiple downstream inflammatory pathways compared to earlier biologics focused on single cytokines like IL-4 or IgE. Ongoing studies aim to clarify long-term benefits and expand therapeutic applications.