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

Cosway, Emilie J; James, Kieran D; White, Andrea J; Parnell, Sonia M; Bacon, Andrea; McKenzie, Andrew N J; Jenkinson, W E; Anderson, Graham · Nat Commun · 2023

basic_science · Level V

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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<sup>+</sup> 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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