A dormant T cell population with autoimmune potential exhibits low self-reactivity and infiltrates islets in type I diabetes
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ABSTRACT:
PROVIDER: PRJNA543305 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR9071890_1.fastq.gz | Fastqsanger.gz | |||
| SRR9071890_2.fastq.gz | Fastqsanger.gz | |||
| SRR9071891_1.fastq.gz | Fastqsanger.gz | |||
| SRR9071891_2.fastq.gz | Fastqsanger.gz | |||
| SRR9071882_1.fastq.gz | Fastqsanger.gz |
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Project description:T cells have been established as the key drivers of autoimmune diabetes. However, it is unknown whether all T cells that infiltrate the pancreas are equally pathogenic, and how the level of reactivity for self-antigen modulates differentiation and pathogenic potential of effector T cells. Moreover, the contribution of bystander, non-antigen reactive T cells in islet autoimmunity has not been resolved. Using multi-color flow cytometry in combination with Nur77-GFP reporter of TCR signaling we identified a “dormant” population of CD4+ T cells that infiltrate the islets of pre-diabetic NOD mice and constitute a significant proportion of all islet infiltrating T cells (~47%). We analyzed TCR repertoire, transcriptional profile, effector function, and autoimmune potential of this subpopulation. This T cell population, characterized by low level expression of CD5 and a unique TCR repertoire, exhibited central memory phenotype with reduced activation and effector function; however, induced rapid diabetes upon transfer. Overall, our study suggests that the strength of reactivity for tissue antigen dictates the level of T cell activation and differentiation; however, cells with low level of TCR signaling and reactivity for islet antigen infiltrating the pancreas of NOD mice are pathogenic and are capable of inducing beta cell destruction.
2019-05-17 | GSE131345 | GEO
Project description:The contribution of low-affinity T cells to autoimmunity in the context of polyclonal T-cell responses is understudied due to the limitations in their capture by tetrameric reagents and low level of activation in response to antigenic stimulation. As a result, low-affinity T cells are often disregarded as nonantigen-specific cells irrelevant to the immune response. Our study aimed to assess how the level of self-antigen reactivity shapes T-cell lineage and effector responses in the context of spontaneous tissue-specific autoimmunity observed in NOD mice. Using multicolor flow cytometry in combination with Nur77GFP reporter of TCR signaling, we identified a dormant population of T cells that infiltrated the pancreatic islets of prediabetic NOD mice, which exhibited reduced levels of self-tissue reactivity based on expression of CD5 and Nur77GFP . We showed that these CD5low T cells had a unique TCR repertoire and exhibited low activation and minimal effector function; however, induced rapid diabetes upon transfer. The CD4+ CD5low T-cell population displayed transcriptional signature of central memory T cells, consistent with the ability to acquire effector function post-transfer. Transcriptional profile of CD5low T cells was similar to T cells expressing a low-affinity TCR, indicating TCR affinity to be an important factor in shaping CD5low T-cell phenotype and function at the tissue site. Overall, our study suggests that autoimmune tissue can maintain a reservoir of undifferentiated central memory-like autoreactive T cells with pathogenic effector potential that might be an important source for effector T cells during long-term chronic autoimmunity.
| S-EPMC9673076 | biostudies-literature
Project description:RNA was sequenced from meristems excised from dormant and non-dormant potato tubers harvested from four different harvest years. Expression based on mapped RNA-sequences was accomplished from excised meristems from fall harvested (dormant tubers) and the same harvested tubers were stored under standard commercial conditions until sprouting was present (non-dormant). The experiment was replicated for four different harvest years.
2014-09-24 | E-GEOD-61690 | biostudies-arrayexpress
Project description:Metastatic relapse frequently develops from disseminated cancer cells that remain dormant in distant organs after the apparently successful treatment of a primary tumor. Disseminated cancer cells fluctuate between immune evasive quiescent and cell cycle reentry states, which exposes them to elimination by the immune system. Little is known about the molecules that determine immune-mediated clearing of awakened metastatic cells and how this process could be therapeutically activated to eliminate residual disseminated disease in patients. Here, we use models of indolent metastasis to identify cancer cell-intrinsic determinants of immune reactivity during cancer cell exit from dormancy. Through in vivo genetic screens of tumor-intrinsic immune regulators, we identified the STING (stimulator of interferon genes) pathway as a suppressor of metastatic outbreak in dormant models of human and mouse lung adenocarcinoma metastasis. STING levels and signaling activity rise in metastatic progenitors that reenter the cell cycle and are dampened by STING enhancer hypermethylation in breakthrough metastases or enhancer chromatin repression in cells reentering dormancy in response to TGF-β. STING expression in cancer cells from spontaneous metastases suppresses their outgrowth in a NK cell- and CD8+ T cell-dependent manner. Systemic treatment of mice with pharmacologic STING agonists eliminates indolent metastatic cells and prevents spontaneous metastasis, both effects requiring cancer cell STING function. Thus, STING signaling represents a checkpoint against the progression of dormant metastasis and suggests a therapeutically actionable strategy for the prevention of disease relapse. Chromatin immunoprecipitation DNA-sequencing (ChIP-seq) for histone modification markers H3K4me1, H3K4me3, H3K27ac in human lung cancer cells at different stages of metastasis and in cells treated with TGF-β or not.
2023-01-30 | GSE210946 | GEO
Project description:We used Illumina RNA-Seq technology to carry out digital gene expression profiling of Dormant and non dormant buds of Shine Muscat Cultivar.127 pathways were annotated by Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and metabolic, biosynthesis of secondry metabolite and. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis demonstrated that DEGs were involved in various metabolic processes, including phytohormone metabolism. The newly generated transcriptome and gene expression profiling data provide valuable genetic information for revealing transcriptomic variation during dormant and non dormant period in Grapevine and ultimately helpful in uplifting of table grape industry.
2017-03-08 | GSE77119 | GEO
Project description:Cellular dormancy and heterogeneous cell cycle lengths provide important explanations for treatment failure following adjuvant therapy with S-phase cytotoxics in colorectal cancer (CRC) yet the molecular control of the dormant versus cycling state remains unknown. In CRCs dormant cells are found to be highly clonogenic and resistant to chemotherapies. We sought to understand the molecular features of dormant CRC cells to facilitate rationale identification of compounds to target both dormant and cycling tumour cells.
2018-05-21 | GSE114012 | GEO
Project description:RNA was sequenced from meristems excised from dormant and non-dormant potato tubers harvested from four different harvest years.
2014-09-24 | GSE61690 | GEO
Project description:BACKGROUND: Adoptive transfer of autologous regulatory T cells (Tregs) is a promising therapeutic strategy aimed at enabling immunosuppression minimization following kidney transplantation. In our phase I clinical trial of Treg cell therapy in living donor renal transplantation, the ONE Study (NCT02129881), we observed focal lymphocytic infiltrates in protocol kidney transplant biopsies that are not regularly seen in biopsies of patients receiving standard immunosuppression. METHODS: We present seven years of follow-up data on patients treated with adoptive Treg cell therapy early post-transplantation, who exhibited focal lymphocytic infiltrates on a nine-month protocol biopsy. We phenotyped their adoptively transferred and peripherally circulating Treg compartments using CITEseq and investigated the focal lymphocytic infiltrates with spatial proteomic and transcriptomic technologies. FINDINGS: Graft survival rates were not significantly different between Treg-treated patients and the control reference group. None of the Treg-treated patients experienced clinical rejection episodes or developed de novo donor-specific antibodies, and three of ten successfully reduced their immunosuppression to tacrolimus monotherapy. All Treg-treated patients who underwent a protocol biopsy nine months post-transplantation exhibited focal lymphocytic infiltrates. Spatial profiling analysis revealed a prominent CD20+ B cell signature within cell therapy-associated immune infiltrates, distinct from the pro-inflammatory myeloid signature typically associated with the rejection biopsies. A regulatory gene expression program (IKZF2, IL10, PD-L1, TIGIT) characterized the cell therapy-associated immune infiltrates at a transcriptional level. CONCLUSIONS: We demonstrate for the first time that immune cell infiltrates in transplanted kidneys can occur following adoptive Treg cell therapy in humans, potentially facilitating within-graft T:B cell interactions that promote local immune regulation. FUNDING: 7th EU Framework Programme, Grant/Award Number: 260687; National Institute for Health Research (NIHR).
2024-11-14 | GSE281542 | GEO
Project description:Conidia of Aspergillus niger are characterized by a dormant state and are moderate stress-resistant. Upon contact with a moist substrate, germination of conidia occurs by changing from a dormant stabilized state towards a growing vegetative cell. The RNA expression levels of dormant conidia and conidia that were in various stages of germination were studied. The RNA composition of dormant conidia was substantially different than all the subsequent stages of germination. This indicates that the distinct morphological changes that occur during germination are not correlated with the highest change in the transcriptome. Samples of germinating conidia of Aspergillus niger N402 were taken in triple at 0h (dormant), 2h, 4h, 6h and 8h after inoculation in CM.
2012-03-13 | E-GEOD-36439 | biostudies-arrayexpress
Project description:RNAseq analysis of dormant cells
| PRJNA485987 | ENA