Human IL‑36Ra/IL‑1F5 Antibody

Human Interleukin-36 receptor antagonist protein [IL36Ra; also named interleukin 1 family member 5, IL-1F5, FIL-1 delta  (delta), IL36RN, IL-1HY1, IL-1H3, and IL-1L1] is a member of the IL-1 family of proteins (1‑6). IL-1 family members include IL-1 beta, IL-1 alpha, IL-1ra, IL-18 and IL-1F5-F10 (6, 7). All family members show a 12 beta -strand, beta -trefoil configuration, and all family members are believed to have arisen from a common ancestral gene that underwent multiple duplications (7). The human IL-1F5 gene is in closest proximity to the gene for IL-1ra and is likely a relatively recent duplication of the IL-1ra gene (2, 3). IL-1F5 is synthesized as a 155 amino acid (aa) protein that contains no signal sequence, no prosegment and no potential N-linked glycosylation site(s) (2‑5). Nevertheless, it appears to be secreted as a 17 kDa monomer (5). There is an alternate start site that potentially gives rise to an alternate splice form (5). The translated product, however, has a premature stop codon, resulting in a truncated 16 aa peptide. Human to mouse, full length IL-1F5 has 90% aa identity. Within the family, IL-1F5 is 50% aa identical to IL-1ra, and 32%, 31%, 35%, 37%, 32% and 42% aa identical to IL-1 beta, IL-1F6, F7, F8, F9 and F10, respectively. Cells reported to express IL-1F5 include monocytes, B cells, dendritic cells/Langerhans cells, keratinocytes, and gastric fundus Parietal and Chief cells (1, 8). The receptor for IL-1F5 has not been positively identified. Indirect evidence suggests it is IL-1 Rrp2 and/or IL-1 RAcP (9). In either case, activity association with receptor binding is also unclear. It was initially reported to be an antagonist of IL‑1F9 activity (4, 7). This would be consistent with its hypothesized relationship to IL-1ra. Studies, however, find IL-1F5 antagonist activity difficult to demonstrate (9).