Ullrich, Karen Anne-MarieSchulze, Lisa LouPaap, Eva-MariaMüller, Tanja MartinaNeurath, Markus F.Zundler, Sebastian2020-12-172020-12-172020-12-11Ullrich, K. A.-M., Schulze, L. L., Paap, E.-M., Müller, T. M., Neurath, M. F., & Zundler, S. (2020). Review article - Immunology of IL-12: An update on functional activities and implications for disease. EXCLI Journal, 19, 1563-1589. https://doi.org/10.17179/excli2020-31041611-2156http://hdl.handle.net/2003/3992110.17877/DE290R-21811As its first identified member, Interleukin-12 (IL-12) named a whole family of cytokines. In response to pathogens, the heterodimeric protein, consisting of the two subunits p35 and p40, is secreted by phagocytic cells. Binding of IL-12 to the IL-12 receptor (IL-12R) on T and natural killer (NK) cells leads to signaling via signal transducer and activator of transcription 4 (STAT4) and subsequent interferon gamma (IFN-γ) production and secretion. Signaling downstream of IFN-γ includes activation of T-box transcription factor TBX21 (Tbet) and induces pro-inflammatory functions of T helper 1 (TH1) cells, thereby linking innate and adaptive immune responses. Initial views on the role of IL-12 and clinical efforts to translate them into therapeutic approaches had to be re-interpreted following the discovery of other members of the IL-12 family, such as IL-23, sharing a subunit with IL-12. However, the importance of IL-12 with regard to immune processes in the context of infection and (auto-) inflammation is still beyond doubt. In this review, we will provide an update on functional activities of IL-12 and their implications for disease. We will begin with a summary on structure and function of the cytokine itself as well as its receptor and outline the signal transduction and the transcriptional regulation of IL-12 secretion. In the second part of the review, we will depict the involvement of IL-12 in immune-mediated diseases and relevant experimental disease models, while also providing an outlook on potential translational approaches.enIfADo - Leibniz Research Centre for Working Environment and Human Factors, DortmundEXCLI Journal;Vol. 19 2020https://creativecommons.org/licenses/by/4.0/IL-12TH1 cellsSTAT4ImmunologyCytokinesustekinumab610article (journal)