PMC

In membrane-bound or soluble form IL-1R2 captures IL-1β and IL-1α with high affinity, but not IL-1Ra; it interacts with IL-1RAcp inhibiting the formation of a signalling receptor complex, and with soluble IL-1RAcP, which increases the affinity for IL-1α and IL-1β. In cytosol soluble form, IL-1R2 interacts with pro-IL1α preventing its pro-inflammatory activity during necrosis. In infectious conditions, caspase-1 cleaves IL-1R2 and allows the secretion of IL-1α.

ACKR2 binds with high affinity inflammatory CC chemokines; it signals through β-arrestin and the small GTPase Rac1 activating cytoskeleton rearrangement in order to optimize the chemokine scavenging activity. It is not known if the interaction of ACKR2 with β-arrestin could have an inhibitory function on other signalling pathways.

IL-1R8 inhibits IL-1R1, IL-18 and IL-33 signaling by competing with MyD88 and IRAK recruitment at the TIR domain, thus dampening the signaling pathway leading to NF-kB activation. In addition, in T and epithelial cells, IL-1R8 inhibits IL-1-dependent activation of the mTOR pathway and of MAPK, thus controlling cell proliferation and survival. IL-1R8 is also a co-receptor of IL-18Rα for IL-37, necessary for the activation of an anti-inflammatory signaling pathway that involves inhibition of MAPKs, NF-κB and TAK1, the pseudo-starvational effects on the mTOR pathway, and the activation of STAT3, Mer, PTEN and p62. IL-1R8 also inhibits the activation of TLR-dependent signaling pathways leading to MAPK and NF-kB activation.