Extracellular and intracellular decoys in the tuning of inflammatory cytokines and Toll-like receptors: the new entry TIR8/SIGIRR.

Following the identification of the interleukin (IL)-1 type II receptor as a prototypic decoy receptor, nonsignaling receptors with decoy functions have been identified for members of the IL-1/IL-18, tumor necrosis factor, IL-10, and IL-13 receptor families. Moreover, the silent receptor D6 is a promiscuous decoy and scavenger receptor of inflammatory chemokines. The type II IL-1 decoy receptor also acts as a dominant-negative molecule. Intracellular pathways of inhibition of IL-1 and Toll-like receptor (TLR) signaling have been identified. In particular, recent results suggest that the Toll/IL-1 receptor (TIR) family member TIR8, also known as single immunoglobulin IL-1-related receptor (SIGIRR), is a negative regulator of IL-1 and TLR signaling. Thus, extracellular and intracellular decoys tune the activation of members of the IL-1/TLR receptor family.