Authors: | Ullrich, Karen Anne-Marie Schulze, Lisa Lou Paap, Eva-Maria Müller, Tanja Martina Neurath, Markus F. Zundler, Sebastian |
Title: | Immunology of IL-12 |
Other Titles: | an update on functional activities and implications for disease |
Language (ISO): | en |
Abstract: | As 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. |
Subject Headings: | IL-12 TH1 cells STAT4 Immunology Cytokines ustekinumab |
URI: | http://hdl.handle.net/2003/39921 http://dx.doi.org/10.17877/DE290R-21811 |
Publishers Link: | https://www.excli.de/index.php/excli/article/view/3104 |
Issue Date: | 2020-12-11 |
Rights link: | https://creativecommons.org/licenses/by/4.0/ |
Provenance: | IfADo - Leibniz Research Centre for Working Environment and Human Factors, Dortmund |
Citation: | Ullrich, 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/excli2020-3104 |
Appears in Collections: | Review Articles 2020 |
Files in This Item:
File | Description | Size | Format | |
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excli2020-3104.pdf | DNB | 1.81 MB | Adobe PDF | View/Open |
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