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 eosinophils are an essential part of an intrathymic type 2 immune network that enables thymus recovery following ablative therapy. Within hours of damage, the thymus undergoes CCR3-dependent colonisation by peripheral eosinophils, which re-establishes 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 signalling in thymic stroma, and ILC2 that represent an intrathymic source of IL5, a cytokine that therapeutically boosts thymus regeneration following damage. Collectively, our findings identify an intrathymic network composed of multiple innate immune cells that restores thymus function during re-establishment of the adaptive immune system.