Introduction
Cytokines are key messenger proteins in our body. They play vital roles in regulating inflammation, immune responses, maintaining homeostasis as well as cell-to-cell signaling. Upon relevant stimuli, a wide range of cells secrete cytokines which often elicit either pro- or anti-inflammatory immune responses, thereby acting as efficient immunoregulators. Cytokines generally signal through their cognate cell-surface receptors which assemble into signaling-competent states upon cytokine binding, bringing their intracellular signaling domains into spatial proximity. These domains are non-covalently associated to Janus kinases (JAKs) which activate signal transducer and activator of transcription proteins (STATs). JAK-driven phosphorylation of STATs leads to cytokine-induced gene transcription and subsequent cellular responses.
Of particular interest to us is the interleukin (IL)-12 cytokine family. IL-12 family cytokines have broad immunological functions and are involved in several diseases from cancer to autoimmunity. The IL-12 cytokine family members are uniquely heterodimeric, each consisting of a four-helix bundle α-subunit and an all-β structured β-subunit. This distinguishes them from other cytokines and makes them interesting models for cellular protein biogenesis but also unique targets for therapeutic applications. The different IL-12 family members, most notably IL-12, IL-23, IL-27, and IL-35, arise from a combination of three ɑ-subunits (IL-12ɑ/p35, IL-23ɑ/p19, and IL-27ɑ/p28) and two β-subunits (IL-12β/p40 and Epstein-Barr virus induced gene 3/EBI3). Furthermore, certain IL-12 family subunits act as cytokines themselves, together establishing a complex network of critical immune regulators (see Figure below).
The broad spectrum of immune responses that is controlled by the IL-12 cytokine family makes them highly relevant molecules to study. Using a broad array of in vitro and in vivo techniques, our lab addresses the following key areas:
