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IL-21-mediated non-canonical pathway for IL-1β production in conventional dendritic cells

Author

Listed:
  • Chi-Keung Wan

    (Laboratory of Molecular Immunology and the Immunology Center, National Heart, Lung and Blood Institute, National Institutes of Health)

  • Peng Li

    (Laboratory of Molecular Immunology and the Immunology Center, National Heart, Lung and Blood Institute, National Institutes of Health)

  • Rosanne Spolski

    (Laboratory of Molecular Immunology and the Immunology Center, National Heart, Lung and Blood Institute, National Institutes of Health)

  • Jangsuk Oh

    (Laboratory of Molecular Immunology and the Immunology Center, National Heart, Lung and Blood Institute, National Institutes of Health)

  • Allison B. Andraski

    (Laboratory of Molecular Immunology and the Immunology Center, National Heart, Lung and Blood Institute, National Institutes of Health
    Present address: Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts 02115, USA.)

  • Ning Du

    (Laboratory of Molecular Immunology and the Immunology Center, National Heart, Lung and Blood Institute, National Institutes of Health)

  • Zu-Xi Yu

    (Pathology Core, National Heart, Lung and Blood Institute, National Institutes of Health)

  • Christopher P. Dillon

    (St Jude Children’s Research Hospital)

  • Douglas R. Green

    (St Jude Children’s Research Hospital)

  • Warren J. Leonard

    (Laboratory of Molecular Immunology and the Immunology Center, National Heart, Lung and Blood Institute, National Institutes of Health)

Abstract

The canonical pathway for IL-1β production requires TLR-mediated NF-κB-dependent Il1b gene induction, followed by caspase-containing inflammasome-mediated processing of pro-IL-1β. Here we show that IL-21 unexpectedly induces IL-1β production in conventional dendritic cells (cDCs) via a STAT3-dependent but NF-κB-independent pathway. IL-21 does not induce Il1b expression in CD4+ T cells, with differential histone marks present in these cells versus cDCs. IL-21-induced IL-1β processing in cDCs does not require caspase-1 or caspase-8 but depends on IL-21-mediated death and activation of serine protease(s). Moreover, STAT3-dependent IL-1β expression in cDCs at least partially explains the IL-21-mediated pathologic response occurring during infection with pneumonia virus of mice. These results demonstrate lineage-restricted IL-21-induced IL-1β via a non-canonical pathway and provide evidence for its importance in vivo.

Suggested Citation

  • Chi-Keung Wan & Peng Li & Rosanne Spolski & Jangsuk Oh & Allison B. Andraski & Ning Du & Zu-Xi Yu & Christopher P. Dillon & Douglas R. Green & Warren J. Leonard, 2015. "IL-21-mediated non-canonical pathway for IL-1β production in conventional dendritic cells," Nature Communications, Nature, vol. 6(1), pages 1-12, November.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms8988
    DOI: 10.1038/ncomms8988
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