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Cholinergic regulation of thymocyte negative selection

ABSTRACT: Cholinergic regulation of thymocyte negative selection

PROVIDER: PRJNA1084716 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR28237361_1.fastq.gz	Fastqsanger.gz
	SRR28237361_2.fastq.gz	Fastqsanger.gz
	SRR28237362_1.fastq.gz	Fastqsanger.gz
	SRR28237362_2.fastq.gz	Fastqsanger.gz
	SRR28237363_1.fastq.gz	Fastqsanger.gz

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Cholinergic regulation of thymocyte negative selection

Project description:Acetylcholine (ACh) and its receptors (AChRs) are widely produced by various kinds of immune cells and fine-tune both innate and adaptive immune responses. However, whether cholinergic signaling regulates immune cell development is unclear. Here, we show that mouse CD4+CD8+ double-positive (DP) thymocytes express high levels of a9 nicotinic (n) AChR, and that this receptor controls the negative selection of thymocytes. Knock-out mice lacking a9 nAChR show an altered TCR repertoire and reduced CD4+ and CD8+ T cells in a mixed bone marrow chimera setting. Although thymic tuft cells, B cells, and a portion of T cells were all found to express choline acetyltransferase (ChAT) and so are sources of ACh in mouse thymus, T cell-derived ACh plays a more important regulatory role. Our results thus reveal a new mechanism of immune cell development control that involves lymphocyte-mediated cholinergic signaling.

2025-03-17 | GSE260947 | GEO

Thymocyte Negative Selection

Project description:Fetal thymic organ culture (FTOC) DC2.5 CD4+CD8+ thymocytes from B6g7 or NOD background. 0 or 16 hour after addition of the BDC mimitope Keywords = BDC2.5 FTOC thymocyte Keywords: dose response

2005-04-05 | GSE2128 | GEO

Notch-Induced Endoplasmic Reticulum-Associated Degradation Governs Thymocyte β Selection

Project description:β -selection imposes a considerable demand for new protein synthesis of the newly rearranged Tcrβ gene and the multiple factors that execute the transcriptional and metabolic programs demanded by DN thymocyte proliferation. However, how proteome homeostasis or “proteostasis” is regulated during thymocyte development is largely unknown. Here, we show that the endoplasmic reticulum (ER)- associated degradation (ERAD), but not the unfolded protein response (UPR), is the master regulator of physiological ER proteostasis in immature DN thymocytes. The ERAD machinery was critically required for successful β-selection of DN3 thymocytes and consequently, ERAD deficiency impeded αβ T cell development. The Sel1L-Hrd1 complex is the most conserved branch of mammalian ERAD machinery. Deletion of Sel1l impaired DN3 to DN4 thymocyte transition and severely impaired αβ T cell development. Mechanistically, Sel1l deficiency induced unresolved ER stress that triggered thymocyte apoptosis through the PERK pathway. This study revealed the stringent protein quality control through the SEL1L-ERAD pathway is required for successful b-selection and the development of the ab T cells that mediate adaptive immunity.

2021-05-07 | GSE173993 | GEO

Mus musculus

Project description:Thymocyte Negative Selection

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Notch-Induced Endoplasmic Reticulum-Associated Degradation Governs Thymocyte β Selection

Project description:Notch-Induced Endoplasmic Reticulum-Associated Degradation Governs Thymocyte β Selection

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Gene expression analysis of thymocyte subsets

2011-08-10 | GSE31082 | GEO

Transcriptional Regulation by NFATc1 during murine thymocyte development

Project description:Transcriptional Regulation by NFATc1 during murine thymocyte development

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A double negative thymocyte specific enhancer augments Notch1 signaling to direct early T cell progenitor expansion, lineage restriction and -selection.

Project description:A double negative thymocyte specific enhancer augments Notch1 signaling to direct early T cell progenitor expansion, lineage restriction and -selection.

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Stress regulation of sustained attention and the cholinergic attention system

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Gene expression analysis of thymocyte subsets

Project description:Mouse thymocytes can be classified into four major subsets based on expression of CD4 and CD8 co-receptors. CD4-CD8- (double negative, DN) cells become CD4+CD8+ (double positive, DP) cells following productive T cell receptor (TCR) beta chain rearrangement. A small proportion of DP cells are selected through interaction of clonal TCRalpha/beta and MHC self peptide complex expressed on thymic stromal cells. DP cell expressing MHC class I-restricted TCR become CD4-CD8+ cells, which will finally differentiate into cytotoxic T cells, while MHC class II restricted selection generates CD4+CD8- helper lineage T cells. We used microarrays to identify genes important for thymocyte differentiation and lineage determination by profiling gene expression in different thymocyte subsets. Mouse thymocytes were divided into four subsets based on CD4, CD8a, and TCRb expression and purified by flw cytometry. FACS purified DN (CD4-CD8a-TCRb-), DP (CD4+CD8a+), CD4SP (CD4+CD8a-TCRbhi) and CD8SP (CD4-CD8a+TCRbhi) populations were lysed in Trizol, and provided to the Genomics Core Facility of the Memorial Sloan-Kettering Cancer Center (MSKCC) for quality control, quantification, reverse transcription, labeling and hybridization to MOE430A 2.0 microarray chips (Affymetrix). Arrays were scanned per the manufacturer’s specifications for the Affymetrix MOE430v2 chip.

2011-08-09 | E-GEOD-31082 | biostudies-arrayexpress

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