Tuft cells and fibroblasts promote thymus regeneration through activation of a type-2 immune response [ILC2_after_Dex]
Ontology highlight
ABSTRACT: The goal of this study was to understand the role of thymic innate lymphoid cells (ILC2) in thymic regeneration following dexamethasone-induced acute involution, and determine whether this is activated by the alarmins IL-25 and IL-33. For this purpose we treated WT, Il25 KO or Il33 mice with dexamethasone, sorted ILC2 cells from their thymi 3 days after treatment when the thymus begins its recovery, or at an earlier time point (18 hours) for comparison, and performed bulk RNA-Seq.
Project description:The goal of this study was to understand the role of thymic innate lymphoid cells (ILC2) in thymic regeneration following irradiation-induced acute involution, and determine whether this is activated by the alarmin IL-25. For this purpose we treated WT or Il25 KO mice with sublethal irradiation and/or recombinant IL-25, sorted ILC2 cells from their thymi 3 days after treatment when the thymus begins its recovery, and performed bulk RNA Seq.
Project description:The goal of this study was to understand the role of thymic tuft cells in thymic regeneration following dexamethasone-induced acute involution, and determine whether this is affected by IL-13, which is produced by ILC2 upon involution and the receptor for which is expressed by tuft cells. For this purpose we treated WT and Il13ra1 KO mice with dexamethasone, sorted tuft cells from their thymi 3 days after treatment when the thymus begins its recovery, at an earlier time point (18 hours) for comparison, or at a later time point (6d) when IL-13 has been released, and performed bulk RNA Seq.
Project description:The goal of this study was to determine whether thymic innate lymphoid cells type-2 (ILC2) activation during acute thymic involution is mediated by the alarmins IL-25 and IL-33. For this purpose we sorted thymic ILC2 from WT mice, treated them ex vivo with recombinant IL-25/IL-33 or both for 24 hours, and performed bulk RNA Seq.
Project description:The goal of this study was to determine whether the alarmin IL-25 has an effect on thymic innate lymphoid cells type-2 (ILC2) at steady state. For this purpose we sorted thymic ILC2 from WT or Il25 KO mice and performed bulk RNA-Seq.
Project description:The goal of this study was to understand the role of thymic natural killer T cells (NKT) in thymic regeneration following dexamethasone-induced acute involution. For this purpose we treated WT mice with dexamethasone, sorted NKT from their thymi 3 days after treatment when the thymus begins its recovery, or at an earlier time point (18 hours) for comparison, and performed bulk RNA Seq.
Project description:The goal of this study was to understand the role of fibroblasts in thymic regeneration following dexamethasone-induced acute involution. For this purpose we treated WT mice with dexamethasone, sorted fibroblasts from their thymi 4 days after treatment when the thymus begins its recovery, or at an earlier time point (18 hours) for comparison, and performed bulk RNA Seq.
Project description:The goal of this study was to determine whether thymic tuft cells activation during acute thymic involution is mediated by IL-13, which is produced by ILC2 upon involution and the receptor for which is expressed by tuft cells. For this purpose we sorted thymic tuft cells from WT mice, treated them ex vivo with recombinant IL-13 for 24 hours, and performed bulk RNA-Seq.
Project description:The goal of this study was to determine how thymic epithelial cells (TEC) differentiation and gene expression is affected by amphiregulin (AREG), which is produced by ILC2 upon thymic involution and the receptor for which is expressed by early TEC subsets. For this purpose we treated WT mice with recombinant AREG, sorted TEC from their thymi 10 days after treatment when the thymus is recovering and AREG has been released, and performed bulk RNA-Seq.
Project description:The tuft cell–ILC2 circuit orchestrates rapid type 2 responses upon detecting microbe-derived succinate and luminal helminths. Our findings delineate key mechanistic steps, involving IP3R2 engagement and Ca2+ flux, governing IL-25 production by tuft cells triggered by succinate detection. While IL-17RB plays a pivotal intrinsic role in ILC2 activation, it exerts a regulatory function in tuft cells. Tuft cells exhibit constitutive Il25 expression, placing them in an anticipatory state that facilitates rapid production of IL-25 protein for ILC2 activation. Tuft cell IL-17RB is crucial for restraining IL-25 bioavailability, preventing excessive tonic ILC2 stimulation due to basal Il25 expression. Suboptimal ILC2 stimulation by IL-25 resulting from tuft cell Il17rb-deficiency or prolonged succinate exposure induces a state of hypoproliferation in ILC2s, also observed in chronic helminth infection. Our study offers critical insights into the regulatory dynamics of IL-25 in this circuit, highlighting the delicate tuning required for responses to diverse luminal states.
Project description:The goal of this study was to understand the role of thymic tuft cells in thymic regeneration following irradiation-induced acute involution. For this purpose we treated WT mice with sublethal irradiation, sorted tuft cells from their thymi 3 days after treatment when the thymus begins its recovery, and performed bulk RNA Seq.