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 and Graham Anderson ()
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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

Nature Communications, 2023, vol. 14, issue 1, 1-11

Abstract: 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.

Date: 2023
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DOI: 10.1038/s41467-023-43072-x

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