IL-33

IL-33 is an IL-1 family cytokine that signals through ST2/IL1RL1, activates NF-κB and MAP kinase pathways, and induces T_H2-associated cytokine production^[1]. Mechanistically, IL-33 links epithelial or endothelial tissue damage to inflammatory signaling because released IL-33 engages ST2-expressing immune cells and amplifies type 2 immune responses^[1][1]. In asthma, alternative IL33 transcript splicing generates IL-33 isoforms that activate basophils and mast cells, supporting type 2 inflammation in chronic stable asthma^[1]. Compared with full-length nuclear IL-33, the natural IL33Δ34 isoform lacks nuclear targeting, accumulates in the cytoplasm, and undergoes tonic apical secretion through exosome-associated trafficking in airway basal cells^[2]. Therefore, isoform selection matters in IL-33 research because altered localization and secretion can change experimental readouts in airway disease models^[1][2]. For inhibitor studies, anti-IL-33 antibodies such as tozorakimab neutralize IL-33^red-ST2 signaling and prevent IL-33^ox-associated RAGE/EGFR signaling, providing tools to test IL-33-dependent inflammation and epithelial dysfunction^[3].