IL-23: changing the verdict on IL-12 function in inflammation and autoimmunity

IL-12 and IL-23 are molecules mainly produced by activated accessory and antigen-presenting cells. The tools for studying the biology of IL-12 in man and laboratory rodents have greatly advanced our appreciation of the central role of this molecule in cell-mediated immunity and inflammation. In particular, IL-12 is thought to be the prime-regulator of TH1 development. Targeting what was thought to be IL-12 function in vivo, resulted in drastic amelioration of inflammation and autoimmunity firmly linking TH1 polarisation to autoimmune development. Upon discovery of IL-23 and the fact that the large subunit of IL-23 is shared by IL-12, the research community only begins to grasp that the features attributed to IL-12 and TH1 development in inflammation are, in fact, dependent on IL-23 and not on IL-12. Hence, the perception of IL-12 biology is, to a large extent, based on a mistaken identity. In this review, the authors provide an overview of their current understanding of IL-12 and IL-23 biology in inflamma...