STAT5 inhibition abrogate TSLP-induced homeostatic maturation of human cDC2s
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE282671 | GEO | 2026/02/23
REPOSITORIES: GEO
Similar Datasets
Project description:To test whether TSLP triggers the homeostatic maturation program of human splenic cDC2 (DC2hm program) in vitro, we administrated TSLP to in-culture human splenic cDC2 and performed RNA-seq. The results showed that TSLP induced DC2hm-like profile including the upregualtion of genes related to DC maturation, migration, immunoregulation, Treg induction and did not induce drastic ISG upregulation compared to either freshly isolated or cDC2s cultured in medium.
2026-02-23 | GSE282579 | GEO
Project description:STAT5 inhibition abrogate TSLP-induced homeostatic maturation of human cDC2s
| PRJNA1189580 | ENA
Project description:To test whether TSLP triggers homeostatic maturation of human cDC2s in vivo, we administrated human TSLP to humanized mice and performed scRNA-seq. We found that TSLP administration increased the proportion of homeostatically matured DC (DC2hm) subtype in cDCs.
2026-02-23 | GSE289224 | GEO
Project description:To explore whether co-expression of CCR7 and IL7R can better define DC2hm (homeostatically matured cDC2) than either marker alone. We sorted IL7R-CCR7+, IL7R+CCR7-, IL7R+CCR7+ DCs as well as CD141+ cDC1 and CD1c+ cDC2 from Lin-CD11c+HLA-DR+ splenocytes of 4 healthy donors and performed bulk RNA-seq. The results showed that the IL7R+CCR7+ double-positive subset showed the highest expression of DC2hm markers among the five subpopulations, supporting the hypothesis that combining CCR7 and IL7R better defines DC2hm.
2026-02-23 | GSE287912 | GEO
Project description:To depict a comprehensive atlas of human splenic DCs and investigate DC2hm in a broad context, we performed Cellular Indexing of Transcriptomes and Epitopes by Sequencing (CITE-seq) using a panel of 151 oligo-conjugated antibodies recognizing surface proteins on Lin [CD3/CD19/NKp46]⁻CD66b⁻ CD88⁻CD89⁻HLA-DR⁺ splenocytes from two donors. This dataset identified nearly all currently recognized human splenic DC subsets. Integrated transcriptomic- and protein-level analyses support the conclusion that DC2hm represents a homeostatic maturation state originating from cDC2 and is distinct from other DC lineages.
2026-02-23 | GSE313153 | GEO
Project description:TSLP administration promotes homeostatic maturation of human cDC2
| PRJNA1189164 | ENA
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
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
Project description:The ontogeny of human Langerhans cells (LCs) remains poorly characterized, in particular the nature of LC precursors and the factors that may drive LC differentiation. Through a systematic transcriptomic analysis of TSLP-activated dendritic cells (DCs), we unexpectedly identified markers that have been associated with a skin-homing potential as well as with a LC phenotype. We performed transcriptomic analysis of TSLP-activated blood DCs, as compared to freshly purified, Medium-, and TNF-activated DCs. Among TSLP up-regulated genes, we identified molecules associated with skin homing, LC phenotype, and LC function, as determined by a literature-based survey. Conversely, genes not expressed in LCs were not found among TSLP-induced genes. Further experiments showed that TGF-? synergized with TSLP leading to the differentiation of blood BDCA-1+ DCs into bona fide Birbeck granule-positive LCs. The ontogeny of human Langerhans cells (LCs) remains poorly characterized, in particular the nature of LC precursors and the factors that may drive LC differentiation. Through a systematic transcriptomic analysis of TSLP-activated dendritic cells (DCs), we unexpectedly identified markers that have been associated with a skin-homing potential as well as with a LC phenotype. We performed transcriptomic analysis of TSLP-activated blood DCs, as compared to freshly purified, Medium-, and TNF-activated DCs. Among TSLP up-regulated genes, we identified molecules associated with skin homing, LC phenotype, and LC function, as determined by a literature-based survey. Conversely, genes not expressed in LCs were not found among TSLP-induced genes. Further experiments showed that TGF-? synergized with TSLP leading to the differentiation of blood BDCA-1+ DCs into bona fide Birbeck granule-positive LCs. Dendritic cells (DC) were purified from the blood of healthy human donors. Each replicate comes from a different donor. There are 6 freshly purified samples (Control_0h), 4 DC samples cultured during 6h with no additional stimulus than the medium (Control_6h), 5 samples cultured during 6h with recombinant TSLP (Thymic Stromal Lymphopoietin at 20 ng/uL) (TSLP_6h) and 3 samples cultured during 6h with recombinant TNF (Tumor necrosis factor at 20 ng/mL) (TNF_6h).
2014-08-01 | E-GEOD-59237 | biostudies-arrayexpress
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