IL‑27 R alpha (also known as WSX‑1 and TCCR) is a 96‑100 kDa member of the type I, group 2 cytokine receptor family (1 - 6). Mature IL‑27 R alpha  is a type I transmembrane glycoprotein that contains a 484 amino acid (aa) extracellular region, a 21 aa transmembrane segment and a 99 aa cytoplasmic domain. Consistent with type I cytokine receptors, the extracellular region contains four positionally conserved cysteine residues, a WSxWS motif (for receptor folding and ligand binding), and three fibronectin type III repeats. The intracellular domain contains a "box‑1" motif that may be involved with Janus kinases (3). One potential alternate splice form has been hypothesized that involves a 58 aa addition to the cytoplasmic domain and, based on mouse, a soluble 33 kDa splice form that shows a 20 aa substitution for aa 257‑636 may also occur in human (3, 7). The human IL‑27 R alpha extracellular region shares 63% amino acid identity with the mouse IL‑27 R alpha extracellular domain (2, 3). IL‑27 R alpha is expressed in mast cells, endothelial cells, NK cells, macrophages, monocytes, B cells, dendritic cells, and naïve T cells (1, 2, 4, 8). Typical of other class I cytokine receptor chains, the ligand binding IL‑27 R alpha molecule is known to heterodimerize with a signal‑transducing subunit (gp130) to form a functional IL‑27 receptor (9, 10). In addition, IL‑27 R alpha is reported to complex with CNTFR alpha and gp130 form a humanin receptor on neurons (7, 11), and to complex with gp130 and IL‑6 R to form a receptor for a p28:CLF heterodimeric cytokine on lymphocytes (12). Studies using IL‑27 R alpha /WSX‑1^‑/‑ mice reveal that IL‑27 has the ability to suppress T cell activity during infection, and to mediate an inhibition of both type 1 and type 2 T cell immunity (4, 13, 14). In particular, IL‑27 is known to act on naïve T cells, blocking their differentiation into a Th17 phenotype. Notably, cells committed to a Th17 phenotype, although they express a functional IL‑27 receptor, are unresponsive to the effects of IL‑27 (15). Activated T cells that are CD4⁺ and CD8⁺, and which express the IL‑27 receptor, can be induced by IL‑27 to form a double‑positive CD25⁺ FoxP3^‑ IFN‑ gamma plus IL‑10 secreting phenotype that both promotes and suppresses the inflammatory response (16).