Genome-wide analysis of gene expression within vitiligo mouse skin
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
SUBMITTER: John Harris
PROVIDER: E-GEOD-53147 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2013-12-12 | E-GEOD-53148 | biostudies-arrayexpress
Project description:Vitiligo skin samples with an active inflammatory infiltrate were selected for gene expression profiling in order to identify inflammatory pathways that drive depigmentation in vitiligo. Total RNA was isolated from 10 deidentified human samples from formalin fixed, paraffin-embedded skin, 5 from vitiligo patients and 5 from controls. Control skin was age- and site-matched excision tips without pathology.
2013-12-12 | E-GEOD-53146 | biostudies-arrayexpress
Project description:Myeloid-derived cells comprising the tumor stroma represent a heterogeneous population of cells critical to the structure, function and growth of established cancers. We have recently found that engineering tumor-specific CD8+ T cells to secrete IL-12 (IL-12TD) can lead to striking improvements in T-cell activity against established melanomas in murine models. Surprisingly, IL-12-dependent enhancement of CD8+ T-cell anti-tumor function did not occur through direct ligation of receptors on lymphocytes or NK cells. Instead, IL-12 sensitized host bone marrow-derived tumor-stromal cells, partly through interferon-gamma, to indirectly enhance the effects of adoptively-transferred T cells. Direct presentation of antigen by tumor was not necessary, but MHC class I expression on endogenous cells was essential for IL-12 mediated anti-tumor enhancements. Upon successful treatment with IL-12TD cells, we observed the selective elimination of tumor-infiltrating CD11b+ F4/80+ macrophages, CD11b+/ClassII+/CD11c+ dendritic cells and CD11b+/Ly6C+/Ly6G- but not CD11b+/Ly6C+/Ly6G+ myeloid-derived suppressor cells within regressing lesions. These results are consistent with a model whereby IL-12 triggers the maturation of myeloid-derived cells into competent antigen cross-presenting cells. Licensed recognition of these antigens by effector T cells may in turn trigger the collapse of the tumor stroma and aid in the regression of large vascularized lesions. Samples were collected at 3 days and 7 days from tumors treated in-vivo with no treatment, Mock pmel-1 CD8+ cell treatment, or IL-12 pmel-1 CD8+ cell treatment. There were 4 biological replicates of each sample type. There were a total of 24 samples.
2012-04-22 | E-GEOD-29164 | biostudies-arrayexpress
Project description:The activation of TLR-MyD88 (Toll like receptor- Myeloid differentiation factor 88) signaling within T cells functions as a potent costimulatory signal that boosts antitumor and antiviral responses. However, the molecular mechanisms underlying the costimulatory processes are poorly understood. We compared microarray gene analysis data between TLR1-TLR2 stimulated and unstimulated T cell receptor transgenic âpmelâ and MyD88-/-pmel CD8+ T cells and identified changes in the expression levels of several TNF family members. In particular, TLR-stimulation increased 4-1BB levels in pmel but not in MyD88-/-pmel T cells. A link between 4-1BB and TLR1-TLR2 signaling in CD8+ T cells was highlighted by in fact that 4-1BB-/- T cells exhibited suboptimal responses to TLR1-TLR2 agonist, but responded normally to CD28 or OX40 costimulation. Moreover, blocking 4-1BB signaling with antibodies also hindered the costimulatory effects of the TLR1-TLR2 agonist. The elevated levels of 4-1BB transcripts in TLR1-TLR2âstimulated cells were not due to increased mRNA stability nor increased histone activation but instead were associated with increased binding of p65 and c-Jun to two distinct 4-1BB promoter sites. Combining TLR1-TLR2 ligand with an agonistic anti-4-1BB antibody enhanced the antitumor activity in mice with established melanoma tumors. These studies reveal that the costimulatory effects of TLR1-TLR2 signaling in CD8+ T cells are in part mediated by 4-1BB and are important for mounting an effective antitumor immune response. CD8+ T cells from the B6.Cg-Thy1/Cy Tg(TcraTcrb)8Rest/J mice, referred to as âpmelâ T cells or from MyD88 knockout pmel mice (MyD88â/âpmel) were sorted. pmel and MyD88â/âpmel T cells were activated using MyD88â/â CD8 T cell-depleted splenocytes pulsed with 10ng/ml of mgp100. This was with or without 10µg/ml of Pam3CSK4. pmel or MyD88â/âpmel CD8 T cells were enriched and used for the extraction of RNA used for genomic analysis.
2016-06-14 | E-GEOD-79475 | biostudies-arrayexpress
Project description:Mouse pmel-1 CD8+ T cells were treated with anti-4-1BB antibody, anti-4-1BBL antibody, or combination of both antibodies to see their effect on the T cells.
2023-08-01 | E-MTAB-13053 | biostudies-arrayexpress
Project description:We previously generated the Orex-HA mouse model in which orexin-producing neurons residing in the hypothalamus selectively expressed a model self-antigen, namely hemagglutinin (HA) from the H1N1 influenza virus. In this model the adoptive transfer of in vitro activated HA-specific CD8 T cells leads to the specific loss of orexinergic neurons located in the hypothalamus. To assess the phenotype and investigate the pathogenic mechanisms and the potential tissue-resident properties of autoreactive (HA-specific) CD8 T cells infiltrating the hypothalamus of Orex-HA mice , we performed a single-cell transcriptomic analysis (scRNA-seq) of HA-specific CD8+ T cells isolated from the hypothalamus and the spleen at day 30 after T cell transfer in Orex-HA mice.
2022-04-14 | E-MTAB-11416 | biostudies-arrayexpress
Project description:A time course of OTI CD8 T cells transferred to irradiated syngeneic hosts (or unirradiated hosts as control).
2007-11-02 | E-GEOD-1921 | biostudies-arrayexpress
Project description:To understand why cancer vaccine-induced T cells often fail to eradicate tumors, we studied immune responses in mice vaccinated with gp100 peptide emulsified in incomplete Freund's adjuvant (IFA), commonly used in clinical cancer vaccine trials. After gp100 peptide/IFA vaccination, tumor-specific CD8+ T cells (adoptively transferred from gp100-specific TCR-transgenic pmel-1 mice) accumulated not in tumors but at the persisting, antigen-rich vaccination site. Once there, primed T cells became dysfunctional and underwent antigen-driven, IFN-γ and FasL-mediated apoptosis, resulting in systemic hyporesponsiveness to subsequent vaccination. Provision of anti-CD40 antibody, TLR7 agonist and interleukin-2 (covax) reduced T cell apoptosis but did not prevent vaccination site sequestration. A non-persisting vaccine formulation shifted T cell localization towards tumors, inducing superior anti-tumor activity. Short-lived formulation also reduced systemic T cell dysfunction and promoted memory formation, as shown by gene expression profiling and other measures. Persisting peptide/IFA vaccine depots, currently used to vaccinate cancer patients, can induce specific T cell sequestration at vaccination sites followed by dysfunction and deletion; short-lived depot formulations may overcome these limitations and result in greater therapeutic efficacy of peptide-based cancer vaccines. To study the fate of melanoma-specific CD8+ T cells after peptide vaccination, we tracked T cell receptor-transgenic pmel-1 T cells in mice vaccinated with heteroclitic gp100_25-33 peptide emulsified in IFA. Splenic pmel-1 CD8+ T cells were purified at 6 and 21 days after vaccination with either gp100/IFA/covax or gp100/saline/covax, and then their total RNA was extracted and used for comparison by gene expression profiling.
2013-03-02 | E-GEOD-43929 | biostudies-arrayexpress
Project description:To shed lights on the potential candidate genes and molecular pathways in vitiligo pathomechanism and therapeutics, we compared the transcriptomes between depigmented and normal skin in Ets-1 knockout mice that spontaneously exhibit human vitiligo-like depigmentation. We performed gene expression profiling analysis using data obtained from RNA-seq of 1 depigmented and 1 pigmented skins of Ets-1 KO mice, and 1 normal skins of wild-type mice.
2023-04-15 | E-MTAB-12835 | biostudies-arrayexpress
Project description:Vitiligo is an acquired depigmentation of the skin inducing a marked alteration of the quality of life of affected individuals. Halting the disease progression and repigmenting the lesional skin represent the two faces of the therapeutic challenge in vitiligo. So far, none of them has been successfully addressed. Oxidative stress and immune system in genetically predisposed individuals participate to the complex pathophysiology of vitiligo. We performed a transcriptome and proteomic analysis on lesional, perilesional and non-depigmented skin of vitiligo patients compared to matched skin controls of healthy subjects. Our results show that the WNT pathway, implicated in melanocytes differentiation, was found to be altered in vitiligo skin. We demonstrated that the oxidative stress decreases WNT expression/activation in keratinocytes and in melanocytes. We developed an ex vivo skin model that remains functional up to 15 days. We then confirmed the decreased activation of the WNT pathway in human skin subjected to oxidative stress. Finally, using pharmacological agents that activate the WNT pathway, we treated the ex vivo depigmented skins from vitiligo patients and successfully induced the differentiation of resident stem cells into pre-melanocytes supporting further exploration of WNT activators to repigment vitiligo lesions. Total of 40 chips. 10 patients (3 biospies per patient: 1 lesional , 1 perilesional and 1 non lesional) ; 10 healthy volunteers (1biopsy in matched anatomical areas)
2015-10-01 | E-GEOD-65127 | biostudies-arrayexpress