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The alarmin IL33 orchestrates type 2 immune-mediated control of thymus regeneration

Author

Listed:
  • Emilie J. Cosway

    (University of Birmingham)

  • Kieran D. James

    (University of Birmingham)

  • Andrea J. White

    (University of Birmingham)

  • Sonia M. Parnell

    (University of Birmingham)

  • Andrea Bacon

    (University of Birmingham)

  • Andrew N. J. McKenzie

    (MRC Laboratory of Molecular Biology)

  • W. E. Jenkinson

    (University of Birmingham)

  • Graham Anderson

    (University of Birmingham)

Abstract

As the primary site of T-cell development, the thymus dictates immune competency of the host. The rates of thymus function are not constant, and thymus regeneration is essential to restore new T-cell production following tissue damage from environmental factors and therapeutic interventions. Here, we show the alarmin interleukin (IL) 33 is a product of Sca1+ thymic mesenchyme both necessary and sufficient for thymus regeneration via a type 2 innate immune network. IL33 stimulates expansion of IL5-producing type 2 innate lymphoid cells (ILC2), which triggers a cellular switch in the intrathymic availability of IL4. This enables eosinophil production of IL4 to re-establish thymic mesenchyme prior to recovery of thymopoiesis-inducing epithelial compartments. Collectively, we identify a positive feedback mechanism of type 2 innate immunity that regulates the recovery of thymus function following tissue injury.

Suggested Citation

  • Emilie J. Cosway & Kieran D. James & Andrea J. White & Sonia M. Parnell & Andrea Bacon & Andrew N. J. McKenzie & W. E. Jenkinson & Graham Anderson, 2023. "The alarmin IL33 orchestrates type 2 immune-mediated control of thymus regeneration," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-43072-x
    DOI: 10.1038/s41467-023-43072-x
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    References listed on IDEAS

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    1. Thomas Venables & Ann V. Griffith & Alice DeAraujo & Howard T. Petrie, 2019. "Dynamic changes in epithelial cell morphology control thymic organ size during atrophy and regeneration," Nature Communications, Nature, vol. 10(1), pages 1-15, December.
    2. Wong Yu & Hitoshi Nagaoka & Mila Jankovic & Ziva Misulovin & Heikyung Suh & Antonius Rolink & Fritz Melchers & Eric Meffre & Michel C. Nussenzweig, 1999. "Continued RAG expression in late stages of B cell development and no apparent re-induction after immunizion," Nature, Nature, vol. 400(6745), pages 682-687, August.
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