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

Emilie J. Cosway, Kieran D. James, Andrea J. White, Sonia M. Parnell, Andrea Bacon, Andrew N. J. McKenzie, W. E. Jenkinson, Graham Anderson*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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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.

Original languageEnglish
Article number7201
Number of pages11
JournalNature Communications
Volume14
Issue number1
DOIs
Publication statusPublished - 8 Nov 2023

Bibliographical note

Acknowledgements:
The authors thank BMSU staff for expert animal husbandry. We also thank Prof Hans Reimer Rodewald for Il7raCre mice, and the NIH Tetramer Facility for mCD1d-PBS57 tetramers. This work was supported by an MRC Programme Grant to GA (MR/T029765/1). A.N.J.M. is supported by the Medical Research Council, as part of United Kingdom Research and Innovation (UK Research and Innovation) (MRC grant U105178805).

Copyright:
© 2023. The Author(s).

Keywords

  • Interleukin-33
  • Alarmins
  • Immunity, Innate
  • Interleukin-4
  • Lymphocytes

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