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Chromatin regulates IL-33 release and extracellular cytokine activity

Author

Listed:
  • Jared Travers

    (Cincinnati Children’s Hospital Medical Center)

  • Mark Rochman

    (Cincinnati Children’s Hospital Medical Center)

  • Cora E. Miracle

    (Cincinnati Children’s Hospital Medical Center)

  • Jeff E. Habel

    (Cincinnati Children’s Hospital Medical Center)

  • Michael Brusilovsky

    (Cincinnati Children’s Hospital Medical Center)

  • Julie M. Caldwell

    (Cincinnati Children’s Hospital Medical Center)

  • Jeffrey K. Rymer

    (Cincinnati Children’s Hospital Medical Center)

  • Marc E. Rothenberg

    (Cincinnati Children’s Hospital Medical Center)

Abstract

IL-33 is an epithelium-derived, pro-inflammatory alarmin with enigmatic nuclear localization and chromatin binding. Here we report the functional properties of nuclear IL-33. Overexpression of IL-33 does not alter global gene expression in transduced epithelial cells. Fluorescence recovery after photobleaching data show that the intranuclear mobility of IL-33 is ~10-fold slower than IL-1α, whereas truncated IL-33 lacking chromatin-binding activity is more mobile. WT IL-33 is more resistant to necrosis-induced release than truncated IL-33 and has a relatively slow, linear release over time after membrane dissolution as compared to truncated IL-33 or IL-1α. Lastly, IL-33 and histones are released as a high-molecular weight complex and synergistically activate receptor-mediated signaling. We thus propose that chromatin binding is a post-translational mechanism that regulates the releasability and ST2-mediated bioactivity of IL-33 and provide a paradigm to further understand the enigmatic functions of nuclear cytokines.

Suggested Citation

  • Jared Travers & Mark Rochman & Cora E. Miracle & Jeff E. Habel & Michael Brusilovsky & Julie M. Caldwell & Jeffrey K. Rymer & Marc E. Rothenberg, 2018. "Chromatin regulates IL-33 release and extracellular cytokine activity," Nature Communications, Nature, vol. 9(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-05485-x
    DOI: 10.1038/s41467-018-05485-x
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