IL-12 Family of Cytokines

IL-12 Cytokine Family: Decipher the Interactions

The Interleukin-12 (IL-12) family of cytokines, which includes IL-12, IL-23, IL-27, and IL-35, are important mediators of inflammatory disease.  Each member is a heterodimeric complex composed of two subunits whose expression is regulated independently.  The founding member, IL-12 (also known as IL-12p70), consists of the heterodimer of p35 and p40.  Moreover, studies have demonstrated that homodimers and monomers of the p40 subunit also exist (known as IL-12p40) and may act as antagonists of IL-12 function.  IL-23 is composed of the heterodimer p40 and p19, which is homologous to p35.  IL-27 is a heterodimeric cytokine consisting of Epstein-Barr virus-induced gene 3 (EBI3) and p28, which are related to p40 and p35, respectively.  The most recently identified member of this family, IL-35, is composed of p35 and EBI3.  As inducers of IFN gamma production, IL-12, IL-23, and IL-27 play critical roles in regulating the inflammatory response.  Moreover, each is involved in mediating T cell-dependent immunity.  For example, IL-12 and IL-27 are involved in T helper 1 (Th1) differentiation, while IL-23 is critical for Th17 survival and expansion.  The functions of IL-35, however, remain to be elucidated.