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

doi:10.1038/s41467-023-43072-x

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

Immunology and Immunotherapy

Research output: Contribution to journal › Article › peer-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 language	English
Article number	7201
Number of pages	11
Journal	Nature Communications
Volume	14
Issue number	1
DOIs	https://doi.org/10.1038/s41467-023-43072-x
Publication status	Published - 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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10.1038/s41467-023-43072-xLicence: Creative Commons: Attribution (CC BY)

CoswayE2023alarminFinal published version, 1.65 MBLicence: Creative Commons: Attribution (CC BY)

Targeting New Mechanisms In The Control Of Thymus Function To Restore Balanced T-cell Production
Anderson, G.
Medical Research Council
1/01/21 → 31/12/25
Project: Research Councils

Cite this

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title = "The alarmin IL33 orchestrates type 2 immune-mediated control of thymus regeneration",

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. ",

keywords = "Interleukin-33, Alarmins, Immunity, Innate, Interleukin-4, Lymphocytes",

author = "Cosway, {Emilie J.} and James, {Kieran D.} and White, {Andrea J.} and Parnell, {Sonia M.} and Andrea Bacon and McKenzie, {Andrew N. J.} and Jenkinson, {W. E.} and Graham Anderson",

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: {\textcopyright} 2023. The Author(s).",

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AU - McKenzie, Andrew N. J.

AU - Jenkinson, W. E.

AU - Anderson, Graham

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AB - 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.

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JO - Nature Communications

JF - Nature Communications

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

Abstract

Bibliographical note

Keywords

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Targeting New Mechanisms In The Control Of Thymus Function To Restore Balanced T-cell Production

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