IL-12 family cytokines: immunological playmakers

Abstract

The interleukin 12 (IL-12) family is unique in having the only heterodimeric cytokines, including IL-12, IL-23, IL-27 and IL-35. This feature endows these cytokines with a unique set of connections and functional interactions not shared by other cytokine families. Despite sharing many structural features and molecular partners, cytokines of the IL-12 family mediate surprisingly diverse functional effects. Here we discuss the unique and unusual structural and functional characteristics of this cytokine family. We outline how cells might interpret seemingly similar cytokine signals to give rise to the diverse functional outcomes that characterize this cytokine family. We also discuss the therapeutic implications of this complexity.

Figure 1. Architecture of the IL-12 Cytokine Family

Diagram shows a schematic of the IL12 family cytokines, their receptors and JAK-STAT signaling partners. The Greed-Red bar along the bottom depicts their functional spectrum from most pro-inflammatory (IL-23) to most inhibitory (IL-35).

Figure 2. IL-12 Family Cytokines as an Immunological Nexus

Depicts the myriad of functional connections and effects mediated by members of the IL-12 cytokine family. Green arrows depict actions that result in pro-inflammatory/pro-stimulatory effects. Red arrows depict actions that result in inhibitory effects. Black arrows depict whether a particular event is up- (↓) or down- (↑) regulated.