Psoriasis is one of the most prevalent T cell-mediated inflammatory disease in humans. It is also listed among the most common autoimmune diseases (Davidson and Diamond, 2001). It, however, shares with chronic inflammatory diseases such as rheumatoid arthritis and Crohn’s disease the absence of a known autoantigen. The pathogenesis of psoriasis is thought to depend on the activation of lesional and/or circulating T cells and their secreted products leading to keratinocyte hyperproliferation and angiogenesis with marked ectasia of blood vessels (Lew et al, 2004; Nickoloff and Nestle, 2004). There is convincing in vitro and in vivo evidence in clinically relevant mouse models and humans that tumor necrosis factor-α (TNF-α) is a master cytokine relevant to the disease process (Chaudhari et al, 2001; Boyman et al, 2004). Yet, the presence of TNF-α does not fully account for the known T helper (Th) 1-dominated cytokine milieu including the presence of ample amounts of interferon-γ (IFN-γ) in lesional psoriatic skin. A key question in psoriasis research relates therefore to factors orchestrating the Th1-immune response in situ. Potential candidates include the interleukin (IL)-12 family members IL-12 and the recently described cytokine IL-23. IL-12 p40 and p35 mRNA as well as p70 protein has been detected in psoriasis lesions (Yawalkar et al, 1998). Recent evidence, however suggests that IL-23, rather than IL-12, might be a key cytokine in psoriatic lesions based on the finding that p19 and p40, but not p35mRNA are increased in psoriatic lesions (Lee et al, 2004).

Both IL-12 and IL-23 are members of the IL-12 family of cytokines sharing a common p40 subunit. p40 forms heterodimers with p35 in IL-12 and p19 in IL-23. IL-12 and IL-23 bind to IL-12Rβ1/IL-12Rβ2 and IL-12Rβ1/IL-23R, respectively. Engagement of IL-23 with its receptor activates a similar spectrum of Janus kinase (JAK)/signal transducer and activator of transcription (STAT) molecules as IL-12 but in contrast to IL-12, the most prominent STAT induced by IL-23 are STAT3/STAT4 heterodimers rather than STAT4 homodimers (Trinchieri et al, 2003). The physiological source of IL-12 and IL-23 are similar. Many cell types express p19 or p35 mRNA, but the relatively restricted expression of p40 subunits limits potential IL-12-and IL-23-producing cells to B cells, monocytes/macrophages and dendritic cells (DC). The receptor complex for IL-12/IL-23 is expressed or