Figure 1

IL-33 release and signaling via ST2L. IL-33 is predominantly expressed by stromal cells such as epithelial and endothelial cells. Damage to these cells can induce necrosis and release of full length IL-33 which can activate the heterodimeric ST2L/IL-1RAcP receptor complex on a variety of immune cells or be neutralized by binding to sST2. During apoptosis IL-33 is cleaved by caspases-3/7 leading to its inactivation. Upon activation of ST2L MyD88 and IRAK-1/4 are recruited and this leads to activation of the transcription factor nuclear factor-κB (NF-κB) and the mitogen-activated protein kinase (MAPK) pathway, which is mediated by the activation of the MAPKs extracellular signal-regulated kinase (ERK), p38 and JUN N-terminal kinase (JNK) and ultimately to the production of Th2 cytokines and chemokines.