Eosinophils are an essential element of a type 2 immune axis that controls thymus regeneration

Emilie J. Cosway; Andrea J. White; Sonia M. Parnell; Edina Schweighoffer; Helen E. Jolin; Andrea Bacon; Hans Reimer Rodewald; Victor Tybulewicz; Andrew N.J. McKenzie; William E. Jenkinson; Graham Anderson

doi:10.1126/sciimmunol.abn3286

Eosinophils are an essential element of a type 2 immune axis that controls thymus regeneration

Emilie J. Cosway, Andrea J. White, Sonia M. Parnell, Edina Schweighoffer, Helen E. Jolin, Andrea Bacon, Hans Reimer Rodewald, Victor Tybulewicz, Andrew N.J. McKenzie, William E. Jenkinson, Graham Anderson^*

^*Corresponding author for this work

Immunology and Immunotherapy

Research output: Contribution to journal › Article › peer-review

7 Citations (Scopus)

Abstract

Therapeutic interventions used for cancer treatment provoke thymus damage and limit the recovery of protective immunity. Here, we show that eosinophils are an essential part of an intrathymic type 2 immune network that enables thymus recovery after ablative therapy. Within hours of damage, the thymus undergoes CCR3-dependent colonization by peripheral eosinophils, which reestablishes the epithelial microenvironments that control thymopoiesis. Eosinophil regulation of thymus regeneration occurs via the concerted action of NKT cells that trigger CCL11 production via IL4 receptor signaling in thymic stroma, and ILC2 that represent an intrathymic source of IL5, a cytokine that therapeutically boosts thymus regeneration after damage. Collectively, our findings identify an intrathymic network composed of multiple innate immune cells that restores thymus function during reestablishment of the adaptive immune system.

Original language	English
Article number	eabn3286
Number of pages	12
Journal	Science Immunology
Volume	7
Issue number	69
DOIs	https://doi.org/10.1126/sciimmunol.abn3286
Publication status	Published - 11 Mar 2022

Bibliographical note

Funding Information:
This work was supported by an MRC Programme Grant to G.A. (MR/T029765/1). E.S. and V.T. were supported by the Francis Crick Institute, which receives its core funding from Cancer Research UK (FC001194), the UK Medical Research Council (FC001194), and the Wellcome Trust (FC001194). This research was funded in whole or in part by The Wellcome Trust, a cOAlition S organization. For the purpose of Open Access, the authors have applied a CC BY public copyright license to any Author Accepted Manuscript version arising from this submission.

Publisher Copyright:
Copyright © 2022 The Authors, some rights reserved.

ASJC Scopus subject areas

Immunology and Allergy
Immunology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1126/sciimmunol.abn3286

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 = "Eosinophils are an essential element of a type 2 immune axis that controls thymus regeneration",

abstract = "Therapeutic interventions used for cancer treatment provoke thymus damage and limit the recovery of protective immunity. Here, we show that eosinophils are an essential part of an intrathymic type 2 immune network that enables thymus recovery after ablative therapy. Within hours of damage, the thymus undergoes CCR3-dependent colonization by peripheral eosinophils, which reestablishes the epithelial microenvironments that control thymopoiesis. Eosinophil regulation of thymus regeneration occurs via the concerted action of NKT cells that trigger CCL11 production via IL4 receptor signaling in thymic stroma, and ILC2 that represent an intrathymic source of IL5, a cytokine that therapeutically boosts thymus regeneration after damage. Collectively, our findings identify an intrathymic network composed of multiple innate immune cells that restores thymus function during reestablishment of the adaptive immune system.",

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Eosinophils are an essential element of a type 2 immune axis that controls thymus regeneration

Abstract

Bibliographical note

ASJC Scopus subject areas

UN SDGs

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

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