Interleukin-36 receptor antagonist (IL-36Ra)

Interleukin-36 receptor antagonist (IL-36Ra, encoded by the IL36RN gene) is a cytokine of the interleukin-1 family functioning as a natural antagonist at the interleukin-36 receptor (IL-36R, also known as IL1RL2). IL-36Ra regulates inflammation primarily in barrier tissues such as the skin by blocking the binding and proinflammatory activity of interleukin-36α, β, and γ. By inhibiting this receptor, IL-36Ra curbs the activation of signaling pathways (notably NF-κB and MAPK) that drive inflammation and immune responses. Loss-of-function mutations in IL36RN cause unregulated skin inflammation, leading to generalized pustular psoriasis, AGEP, and other autoinflammatory conditions; modulation of this pathway is of clinical interest, and IL-36R is the pharmacological target of emerging therapies such as spesolimab.

Other names

Interleukin-36 receptor antagonist proteinIL36RNFIL1DIL1F5IL1HY1IL1L1IL1RP3IL36RAPSORPPSORS14IL-1RP3IL-1HY1IL-1 deltaIL-1F5IL-1ra homolog 1IL-1L1FIL1FIL1(DELTA)Interleukin-1 receptor antagonist homolog 1Interleukin-1 HY1Interleukin-1 deltaInterleukin-1 family member 5Interleukin-1-like protein 1Family of interleukin 1-deltaIL1F5 (Canonical product IL-1F5a)MGC29840FIL1 deltaIL-1 related protein 3

Antagonists bind to IL-36 receptor, preventing IL-36α/β/γ agonists from activating the receptor and blocking downstream inflammatory signaling (inhibition of NF-κB/MAPK pathways). IL-36Ra itself acts as a natural antagonist by competing with agonists for receptor binding