Interleukin 12β and EBI3: Emerging immunomodulatory members of the interleukin 12 family

Cytokines of the interleukin 12 (IL-12) family are secreted by cells of the innate immune system to regulate adaptive immune responses. IL-12 family cytokines are heterodimers composed of an α- and a β-subunit each, with subunits shared between the different family members. It is increasingly becoming clear that, in addition to the family-characteristic heterodimers, the α/β subunits often engage in further pairings and can also regulate immune responses in isolation. Here, we review our current understanding of IL-12β/p40 and EBI3, the two β-subunits within the family. IL-12β/p40 and EBI3 are emerging as critical regulators of immunity in health and disease. They function by forming heterodimeric assemblies but also as monomers and homodimers. Due to this complexity, many open questions remain concerning their molecular structure and assemblies, their receptors and their detailed mode of action. It will be key to address these to seize the therapeutic opportunities of IL-12β/p40 and EBI3 despite their structural and functional complexity.