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Analysis of transcriptional changes induced in TSLP in CD4+ T cells

ABSTRACT: TSLP-stimulated CD4+ T cells block the promotion of breats tumor in mice. In this experiment, we analyze the differences in gene expression profiles of CD4+ T cells in PyMT mice in presence or absence of TSLP-stimulated CD4+ T cell

ORGANISM(S): Mus musculus

PROVIDER: GSE147106 | GEO | 2022/05/15

REPOSITORIES: GEO

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Analysis of transcriptional changes induced in PyMT breast tumor by TSLP stimulated CD4+ T cells

Project description:TSLP-stimulated CD4+ T cells block the promotion of breats tumor in mice. In this experiment, we analyze the differences in gene expression profiles of PyMT breast tumors in presence or absence of TSLP-stimulated CD4+ T cell

2022-05-15 | GSE147067 | GEO

Analysis of the effect of TSLP stimulated CD4+T cells on epigenetic markers in PyMT primary tumors

Project description:TSLP-stimulated CD4+ T cells block the promotion of breast cancer in a spontaneous PyMT mouse model. The goal of this project is to investigate what are the epigenetic changes induced by CD4+ T cells that lead to diminished proliferation of cancer cells

2022-05-15 | GSE156117 | GEO

Analysis of transcriptional changes induced in PyMT breast tumor by TSLP stimulated CD4+ T cells

Project description:Analysis of transcriptional changes induced in PyMT breast tumor by TSLP stimulated CD4+ T cells

| PRJNA612871 | ENA

Programming of a pathogenic Th2 state by TSLP signaling in CD4+ T cells

Project description:Pathogenesis of allergic diseases including asthma is strongly associated with robust responses of allergen-specific Th2 cells, which produce high levels of IL-4, IL-5, IL-9, and IL-13. Despite evidence for pathogenic Th2 cells in the induction and propagation of allergic disorders, signals required for differentiation of such cells remain largely unknown. Thymic stromal lymphopoietin (TSLP) is a cytokine that is expressed upon epithelial injury, dysfunction or infection and is strongly implicated in the pathogenesis of atopic dermatitis (AD) and asthma. Although indirect regulation of Th2 differentiation via TSLP-stimulated dendritic cells well known, direct effects of TSLP on Th2 differentiation in vivo have not been rigorously analyzed. We show that TSLP may initiate Th2 response independent on IL-4 signal and increases sensitivity of CD4 cells to IL-4 stimulation inducing more robust expression of IL-4, IL-5, and IL-13 by human and mouse CD4 cells. This more potent effector state appears to be stably programmed in memory Th2 cells. As part of molecular mechanism, we demonstrate that TSLP and IL-4 signals induce distinctive genome wide alterations in activating histone modification (H3K27Ac, H3K36Me3, and H3K4Me3). We propose that TSLP acts in coordination with IL-4 to generate a more potent Th2 state that could underlie persistence and propagation of allergic disorders.

2017-04-01 | GSE81384 | GEO

Analysis of the effect of TSLP stimulated CD4+T cells on epigenetic markers in PyMT primary tumors

Project description:Analysis of the effect of TSLP stimulated CD4+T cells on epigenetic markers in PyMT primary tumors

| PRJNA656800 | ENA

TSLP Expression: Analysis with a ZsGreen TSLP Reporter Mouse

Project description:Thymic stromal lymphopoietin (TSLP) is a type I cytokine that plays a central role in induction of allergic inflammatory responses. Its principal targets have been reported to be dendritic cells and / or CD4 T cells; epithelial cells are a principal source. We report here the development of a reporter mouse (TSLP-ZsG) in which a ZsGreen (ZsG)-encoding construct has been inserted by recombineering into a bacterial artificial chromosome (BAC) immediately at the translation initiating ATG of TSLP. The expression of ZsG by mice transgenic for the recombinant BAC appears to be a faithful surrogate for TSLP expression, particularly in keratinocytes and medullary thymic epithelials cells (mTECs). A comparison of gene expression in ZsG expressing and ZsG negative mTECs and cortical thymic epithelial cells, which are all ZsG negative, revealed that all three populations can be distinguished from one another. In particular ZsG (and TSLP) expressing mTECs and ZsG- mTECs are separable populations based on gene expression profiling. Little or no expression of ZsG is observed in bone marrow-derived mast cells or basophils or in CD45+ cells infiltrating TSLP/ZsG-expressing skin. Using the TSLP-ZsG reporter mouse, we show that TNFa and IL-4/IL-13 are potent inducers of TSLP expression by keratinocytes and that local activation of Th2 and Th1 cells induces keratinocyte TSLP expression. We suggest that the capacity of TSLP to both induce Th2 differentiation and to be induced by activated Th2 cells raises the possibility that TSLP may be involved in a positive feedback loop to enhance allergic inflammatory conditions.

2015-01-06 | GSE54343 | GEO

Gene expression profiling of naïve bone marrow-resident granulocyte monocyte precursors (GMPs) and TSLP-elicited splenic GMP-like cells

Project description:Extramedullary hematopoiesis (EMH) refers to the differentiation of hematopoietic stem cells (HSCs) into effector cells that occurs in compartments outside of the bone marrow. Previous studies linked pattern recognition receptor (PRR)-expressing HSCs, EMH and immune responses to microbial stimuli. However, the factors that regulate EMH and whether EMH operates in broader immune contexts remain unknown. Here, we demonstrate a previously unrecognized role for thymic stromal lymphopoietin (TSLP) in promoting the population expansion of progenitor cells in the periphery and identify that TSLP-elicited progenitors differentiate into effector cells including macrophages, dendritic cells and granulocytes that contribute to TH2 cytokine responses. The frequency of circulating progenitor cells was also increased in allergic patients with a gain-of-function polymorphism in TSLP, suggesting the TSLP-EMH pathway may operate in human disease. These data identify that TSLP-induced EMH contributes to the development of allergic inflammation and indicate that EMH is a conserved mechanism of innate immunity. In this study, we performed gene expression profiling to examine how the transcriptional signatures compared between TSLP-elcited GMP-like cells and naïve bone marrow-resident GMPs. Splenic TSLP-elicited GMP-like cells (CD3-, CD4-, CD5-, CD8-, CD19-, CD11b-, CD11c-, NK1.1-, FcεRI-, CD34+ c-kit+) were sort-purified from the spleen of C57BL/6 mice on day 5 post-TSLP-cDNA treatment. BM-resident GMPs (CD3-, CD4-, CD5-, CD8-, CD19-, CD11b-, CD11c-, NK1.1-, FcεRI-, Sca1- c-kit+ CD34+ CD16/32+) were sort-purified from mice that received a control-cDNA injection.

2014-03-28 | E-GEOD-52485 | biostudies-arrayexpress

Keratin-dependent TSLP expression suggests a link between skin blistering and atopic disease

Project description:Atopic dermatitis (AD) is a pruritic and inflammatory disorder characterized by elevated levels of thymic stromal lymphopoietin (TSLP). Pruritus is prevalent in epidermolysis bullosa (EB). Currently, epidermal barrier disruption is known to trigger TSLP upregulation, however, mechanisms controlling TSLP expression remain incompletely understood. Tslp levels were highly upregulated in the epidermis and in the serum of keratin-deficient mice. Cultured keratinocytes either lacking keratins or expressing the dominant K14p.Arg131Pro show highly increased TSLP. Re-expression of wild-type K14 normalized TSLP levels. We demonstrate that keratins regulate Tslp expression in parts through MEK1/2 activation. The finding that 8 out of 17 EBS patients show elevated TSLP serum levels supports a major role of keratins in TSLP regulation. Our data identify a novel, keratin-dependent and cell-intrinsic regulation of Tslp. Elevated TSLP levels likely explain the high prevalence of pruritus in EBS and additional forms of EB, suggesting TSLP as novel biomarker for pruritus in EB. MEK1/2, in addition to calcineurin inhibitors, might be suitable drugs to treat itch in EB. Investigation was carried out using Keratin deficient keratinocytes isolated from typeI keratin mice.

2016-03-26 | E-GEOD-79596 | biostudies-arrayexpress

Expression data from skin of mice treated subcutaneously with TGF-beta, IL-13 or TSLP for 7 days

Project description:Gene expression in mice skin stimulated with 3 different cytokines We used microarrays to detail the global programme of specific or common gene expression by 3 cytokines: TGF-beta, IL-13 and TSLP Mice skin were taken from the outlet of the 7-day pump (subcutaneous) and RNA was extracted.

2013-10-31 | E-GEOD-34297 | biostudies-arrayexpress

Analysis of transcriptional changes induced in TSLP in CD4+ T cells

Project description:Analysis of transcriptional changes induced in TSLP in CD4+ T cells

| PRJNA613042 | ENA