ST2 is a member of the Toll-interleukin 1 receptor (TIR) superfamily, expressed by mast cells and TH2 helper cells, but not by TH1 effector cells. The majority of TIR superfamily members, which includes the Interleukin-1 receptor (IL-1R1), Toll-like receptors (TLRs) and the cytosolic adaptor proteins MyD88, TIRAP, Trif and TRAM, initiate innate immunity through the ultimate activation of the transcription factor NF-kappaB and are inducers of the inflammatory response. In contrast ST2, which itself is unable to activate NF-kappaB, has been identified as a negative regulator of IL-1R1 and TLR4 signaling by sequestering MyD88 and TIRAP (1), in line with its role as a crucial receptor in TH2-cell mediated responses (2).