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Tuft cells and fibroblasts promote thymus regeneration through activation of a type-2 immune response [ex_vivo_tuft]

ABSTRACT: 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE244223 | GEO | 2024/01/11

REPOSITORIES: GEO

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Tuft cells and fibroblasts promote thymus regeneration through activation of a type-2 immune response [Tuft_after_Dex]

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.

2024-01-11 | GSE244220 | GEO

Tuft cells and fibroblasts promote thymus regeneration through activation of a type-2 immune response [ex_vivo_ILC2]

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.

2024-01-11 | GSE244222 | GEO

Tuft cells and fibroblasts promote thymus regeneration through activation of a type-2 immune response [ILC2_after_irr]

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.

2024-01-11 | GSE244202 | GEO

Tuft cells and fibroblasts promote thymus regeneration through activation of a type-2 immune response [ILC2_after_Dex]

Project description: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.

2024-01-11 | GSE244216 | GEO

Tuft cells and fibroblasts promote thymus regeneration through activation of a type-2 immune response [TEC_after_rAREG_inj]

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.

2024-01-11 | GSE244225 | GEO

Tuft cells and fibroblasts promote thymus regeneration through activation of a type-2 immune response [Tuft_after_irr]

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.

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Tuft cells and fibroblasts promote thymus regeneration through activation of a type-2 immune response [IL25KO_ILC2_untreated]

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.

2024-01-11 | GSE244224 | GEO

mRNA-seq of thymic epithelial cells from PBS or IL-33 treated thymus

Project description:Severe infection commonly results in T cell aging, which leads to impaired pathogen clearance or increased secondary infection in both humans and animals. However, the exact mechanisms remain poorly understood. Here, we demonstrated that severe infection-induced IL-33 production resulted in acute thymic involution-mediated naive T cell aging and impaired host control of infection in mouse disease models of schistosomiasis or sepsis. Furthermore, we illustrated that IL-33 triggered excessive generation of medullary thymic epithelial cell (mTEC) IV (thymic tuft cells) in a Pou2f3-dependent manner, as a consequence, disturbed mTEC/cortical TEC (cTEC) compartment and caused acute thymic involution during severe infection. More importantly, IL-33 deficiency or IL-33 receptor ST2 deficient thymus transplantation rescued T-cell immunity to better control infection in mice. Our findings not only uncover a novel link between severe infection-induced IL-33 and thymic involution-mediated naive T cell aging, but also suggest that targeting IL-33 or ST2 is a promising strategy to rejuvenate T cell immunity to better control severe infection.

2022-10-23 | GSE189201 | GEO

Loss of Elp3 impairs the immune response to helminths by blocking intestinal tuft cell differentiation

Project description:Intestinal tuft cells are critical in anti-helminth immunity by producing IL-25, which triggers IL-13 secretion by activated group 2 innate lymphoid cells (ILC2s) in order to ultimately expand both goblet and tuft cells. Translational reprogramming is involved in intestinal tuft cell differentiation but the role of tRNA modifications in this process is unknown. We show here that epithelial Elp3, a tRNA-modifying enzyme, promotes tuft cell differentiation and is consequently critical for IL-25 production, ILC2 activation, goblet cell expansion and control of N. brasiliensis infection in mice. Elp3 is essential for the IL-13-dependent induction of some glycolytic enzymes such as Hexokinase 1 and Aldolase A and consequently links specific metabolic pathways to tuft cell differentiation. Importantly, loss of epithelial Elp3 in the intestine blocks the translation of Nprl2, a mTORC1 inhibitor, which consequently enhances mTORC1 activation and stabilizes Atf4 in both transit amplifying and progenitor cells. Likewise, Atf4 overexpression in mouse intestinal epithelium blocks tuft cell differentiation and impairs the control of intestinal helminth infection. Collectively, our data define Atf4 as a negative regulator of tuft cell differentiation and provide insights into mechanisms through which some tRNA modifications promote a type 2 immune response to parasites in the intestine.

2024-07-25 | GSE241625 | GEO

Tuft cells and fibroblasts promote thymus regeneration through activation of a type-2 immune response [NKT_after_Dex]

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.

2024-01-11 | GSE244221 | GEO

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