Interleukin-33 (IL-33) is a dual-function alarmin cytokine in the IL-1 family, critical for tissue homeostasis and immune regulation . Its receptor, ST2 (IL-33R), forms a heterodimer with IL-1RAcP to activate signaling cascades in Th2 cells, ILC2s, and other immune cells . Dysregulation of the IL-33/ST2 axis is implicated in inflammatory diseases, infections, and autoimmune conditions .
Mechanism: Dual inhibition of IL-33 signaling via ST2 and RAGE/EGFR pathways .
Affinity: Femtomolar binding (K<sub>D</sub> = 30 fM for IL-33<sup>red</sup>), surpassing soluble ST2 (sST2) .
Efficacy:
Specificity: Detects 15–30 kDa bands in mouse tissues (spleen, lymph nodes) .
Validation: Knockout controls confirm specificity for IL-33 in murine models .
Target: IL-33 Receptor (ST2) on Th2 cells, eosinophils, and mast cells .
Function: Blocks IL-33 binding, serving as a decoy receptor in soluble form .
Rheumatoid Arthritis (RA): Serum IL-33 correlates with auto-antibody positivity (RF/anti-CCP) but not treatment response :
Systemic Lupus Erythematosus (SLE): Anti-RA33 antibodies associate with high disease activity and mucocutaneous involvement (AUC = 0.634, specificity = 92.9%) .
Respiratory Diseases: IL-33 drives ILC2-mediated eosinophilia and airway hyper-responsiveness in murine models . Neutralizing antibodies reduce epithelial injury and inflammation .
Bacterial Infections: IL-33 enhances neutrophil extracellular trap production against S. aureus and improves macrophage bactericidal activity .
Dual Signaling: IL-33 oxidation state (IL-33<sup>red</sup> vs. IL-33<sup>ox</sup>) requires antibodies like tozorakimab to block both ST2 and RAGE/EGFR pathways .
Biomarker Potential: Serum IL-33 detection lacks prognostic value for biologic therapies in RA but may guide personalized approaches in SLE .
KEGG: cel:CELE_W05H5.6
UniGene: Cel.27955