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IL-27: A Key Player in Immune Regulation

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Interleukin-27: Biological Properties and Clinical Application

Part of the book series: SpringerBriefs in Immunology ((BRIEFSIMMUN))

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Abstract

Interleukin-27 plays an important role in the regulation of immune response. IL-27 signaling mediated by its heterodimeric IL-27Rα/gp130 receptor activates multiple signaling cascades, including STAT1 and STAT3, Akt/mTOR, ERK, and p38 MAPK pathways. Up- and downregulation of both receptor subunits and cross talk between immune cell populations regulate the magnitude of signal transduction. Transduction of IL-27 stimulatory signal is also limited through a reciprocal feedback loop involving SOCS3. Initial studies focused on proinflammatory activities of IL-27. IL-27 induces expression of T-bet and hence promotes Th1 cell differentiation and augments CD8+ T cell- and NK cell-mediated cytotoxicity. Simultaneously, IL-27 limits inflammation through its ability to negatively regulate GATA-3 and ROR-γt, key transcription factors of Th2 and Th17 cells, respectively. In contrast, Tr1 cell differentiation is positively stimulated by IL-27 through upregulation of c-Maf and Ahr further contributing to the limitation of the inflammation. Here, we have discussed the downstream signaling from the IL-27 receptor and its main molecular targets in immune cell subsets including Th1, Th2, Th17, Treg, Tr1, and Tfh cell population as well as B cells, DCs, and macrophages.

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  1. Chair of Dermatology, Sexually Transmitted Diseases and Immunodermatology, Faculty of Medicine, Nicolaus Copernicus University in Toruń, Bydgoszcz, Poland

    Marek Jankowski

  2. Department of Gene Therapy, Faculty of Medicine, Nicolaus Copernicus University in Toruń, Bydgoszcz, Poland

    Tomasz Wandtke

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Jankowski, M., Wandtke, T. (2016). IL-27: A Key Player in Immune Regulation. In: Interleukin-27: Biological Properties and Clinical Application. SpringerBriefs in Immunology. Springer, Cham. https://doi.org/10.1007/978-3-319-39664-4_2

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