Chan Jason R, Blumenschein Wendy, Murphy Erin, Diveu Caroline, Wiekowski Maria, Abbondanzo Susan, Lucian Linda, Geissler Richard, Brodie Scott, Kimball Alexa B, Gorman Daniel M, Smith Kathleen, de Waal Malefyt Rene, Kastelein Robert A, McClanahan Terrill K, Bowman Edward P
Discovery Research, Schering-Plough Biopharma (formerly DNAX Research, Inc.), Palo Alto, CA 94304, USA.
J Exp Med. 2006 Nov 27;203(12):2577-87. doi: 10.1084/jem.20060244. Epub 2006 Oct 30.
Aberrant cytokine expression has been proposed as an underlying cause of psoriasis, although it is unclear which cytokines play critical roles. Interleukin (IL)-23 is expressed in human psoriasis and may be a master regulator cytokine. Direct intradermal administration of IL-23 in mouse skin, but not IL-12, initiates a tumor necrosis factor-dependent, but IL-17A-independent, cascade of events resulting in erythema, mixed dermal infiltrate, and epidermal hyperplasia associated with parakeratosis. IL-23 induced IL-19 and IL-24 expression in mouse skin, and both genes were also elevated in human psoriasis. IL-23-dependent epidermal hyperplasia was observed in IL-19-/- and IL-24-/- mice, but was inhibited in IL-20R2-/- mice. These data implicate IL-23 in the pathogenesis of psoriasis and support IL-20R2 as a novel therapeutic target.
细胞因子表达异常被认为是银屑病的潜在病因，尽管尚不清楚哪些细胞因子起关键作用。白细胞介素（IL）-23在人类银屑病中表达，可能是一种主要调节细胞因子。将IL-23直接皮内注射到小鼠皮肤中，而不是IL-12，会引发一系列肿瘤坏死因子依赖性但IL-17A非依赖性的事件，导致红斑、混合性真皮浸润以及与角化不全相关的表皮增生。IL-23在小鼠皮肤中诱导IL-19和IL-24表达，这两个基因在人类银屑病中也升高。在IL-19基因敲除和IL-24基因敲除小鼠中观察到IL-23依赖性表皮增生，但在IL-20R2基因敲除小鼠中受到抑制。这些数据表明IL-23参与银屑病的发病机制，并支持将IL-20R2作为一个新的治疗靶点。
