Prospects to translate the biology of IL-33 and ST2 during organ transplantation into therapeutics to treat graft-versus-host disease

Interleukin (IL)-33 (also known as IL1F11, NF-HEV) is an IL-1 family cytokine constitutively expressed at endothelial and epithelial barrier surfaces where it is rapidly released from cells during tissue injury (1). IL-33 signals via a receptor complex of ST2 (serum stimulation 2; also known as IL1RL1, DER4, FIT-1, T1, IL33R) and IL-1 receptor accessory protein to initiate and amplify inflammatory responses through activation of NFκB and MAP Kinase signalling pathways (1,2). Due to its rapid action following injury or infection, IL-33 is often referred to as an “alarmin” or endogenous danger signal.