Human Interleukin-31 (IL-31) is a 24 kDa, short-chain member of the alpha -helical family of cytokines. The human IL-31 cDNA encodes a 164 amino acid (aa) precursor that contains a 23 aa signal peptide and a 141 aa mature protein. The mature region shows four alpha -helices which would be expected to show a typical up‑up‑down‑down topology. Human and mouse IL-31 share 24% aa sequence identity in the mature region. IL-31 is mainly associated with activated T cells and preferentially expressed by Th2 rather than Th1 cells. IL-31 signals via a heterodimeric receptor complex composed of a 120 kDa, gp130-related molecule termed IL‑31 RA (also GPL and GLM-R) and the 180 kDa oncostatin M receptor (OSM R beta ). In the complex, IL-31 directly binds to GPL, not OSM R. IL-31 signaling has been shown to involve the Jak/STAT pathway, the PI3 kinase/AKT cascade, and the MAP kinase pathway. Although multiple isoforms of IL-31 RA are known, only a form that contains the