TSLP is released by epithelial cells in response to environmental triggers (allergens, pollutants, viruses) — it is one of the first signals in the inflammatory cascade. TSLP then activates dendritic cells and ILC2s, which in turn drive Th2 differentiation and IL-4/IL-5/IL-13 production. By blocking TSLP, you inhibit the cascade before it diversifies into multiple downstream pathways. This is why Tezepelumab works across all inflammatory phenotypes — including non-eosinophilic asthma where anti-IL-5 (Mepolizumab) and anti-IL-4Rα (Dupilumab) are less effective.

Long-form TSLP (lfTSLP) is the full-length 159 aa inflammatory isoform induced by allergens, IL-1β, and TNF-α. It signals through TSLPR/IL-7Rα and drives type 2 inflammation. Short-form TSLP (sfTSLP) is a 63 aa constitutively expressed isoform with antimicrobial activity against skin pathogens but no inflammatory function — it does not bind TSLPR. Therapeutic anti-TSLP antibodies target the long form. When purchasing recombinant TSLP for functional assays, ensure you are using the long-form isoform.

The standard approach uses monocyte-derived dendritic cells (moDCs) or a TSLP-responsive reporter cell line. Stimulate moDCs with TSLP (10-50 ng/mL) for 24 hours and measure OX40L surface expression (by flow cytometry) or CCL17/TARC secretion (by ELISA). To test neutralization, pre-incubate TSLP with serial dilutions of candidate anti-TSLP antibody before adding to cells. Alternatively, use a STAT5-reporter cell line transfected with TSLPR and IL-7Rα for a higher-throughput format.

Tezepelumab (anti-TSLP) blocks the upstream epithelial signal and is effective across all asthma inflammatory phenotypes. Dupilumab (anti-IL-4Rα) blocks both IL-4 and IL-13 signaling and is most effective in type 2-high (eosinophilic and allergic) asthma and atopic dermatitis. Mepolizumab (anti-IL-5) specifically reduces eosinophil counts and is indicated for severe eosinophilic asthma only. The three therapies target different levels of the inflammatory cascade, and Tezepelumab is the only one without a biomarker-based (eosinophil or IgE) patient selection requirement.

Elevated serum TSLP has been reported in severe asthma, atopic dermatitis, and eosinophilic esophagitis, but serum levels are often low and variable, making TSLP a challenging circulating biomarker. Tissue TSLP expression (IHC in bronchial biopsies or skin biopsies) is more reliable. Our TSLP ELISA kit has a sensitivity of <10 pg/mL to detect the low concentrations typically found in serum. For tissue studies, anti-TSLP IHC antibodies can visualize epithelial TSLP expression patterns.