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Regulation of IL-1 signaling by the decoy receptor IL-1R2

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Abstract

The pleiotropic cytokine IL-1 mediates its biological functions via association with the signaling receptor IL-1R1. Despite an apparent simplicity in IL-1 signaling activation, multiple negative regulators have been identified. The decoy receptor IL-1R2 (also known as CD121b) can suppress IL-1 maturation, sequester its active forms or hinder the signaling complex assembly. IL-1R2 is differentially expressed among numerous cell types and displays cis- and trans- modes of action. In this review, we link different forms of IL-1R2 (membrane-bound (mIL-1R2), secreted (sIL-1R2), shedded (shIL-1R2), cytoplasmic, and intracellular domain (IL-1R2ICD) restricted) with their ability to interfere with IL-1, thereby regulating immune responses. We also discuss the intriguing possible function of IL-1R2 as a transcriptional regulator. Finally, we summarize the known impact of IL-1R2 in disease pathogenesis and discuss its potential role in treatment of inflammatory conditions.

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Acknowledgements

We thank M. Schlüter for the help in figure preparations, C. Dietz and C. Raffin for the critical editing of the manuscript.

Research in the Institute for Molecular Medicine was supported by the Research Centre Immunology (FZI) Mainz and by a grant from the Deutsche Forschungsgemeinschaft (DFG) CRC/TR 156 directed to Ari Waisman. Additionally, I.A.M. received intramural funding (Stufe1) provided by University of Mainz and was supported by Sean N. ParkerAutoimmunity Research Laboratory.

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  1. Institute for Molecular Medicine, University Medical Center of the Johannes Gutenberg-University Mainz, Langenbeckstrasse 1, 55131, Mainz, Germany

    Thomas Schlüter, Carsten Schelmbauer, Khalad Karram & Ilgiz A. Mufazalov

  2. Diabetes Center, University of California, San Francisco, San Francisco, CA 94143, USA

    Ilgiz A. Mufazalov

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  1. Thomas Schlüter
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  2. Carsten Schelmbauer
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  3. Khalad Karram
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  4. Ilgiz A. Mufazalov
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Correspondence to Ilgiz A. Mufazalov.

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Schlüter, T., Schelmbauer, C., Karram, K. et al. Regulation of IL-1 signaling by the decoy receptor IL-1R2. J Mol Med 96, 983–992 (2018). https://doi.org/10.1007/s00109-018-1684-z

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  • DOI: https://doi.org/10.1007/s00109-018-1684-z

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