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Innate-like T cell subset commitment in the murine thymus is independent of TCR characteristics and occurs during proliferation

ABSTRACT: Innate-like T cell subset commitment in the murine thymus is independent of TCR characteristics and occurs during proliferation

PROVIDER: PRJNA991993 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR25180500_1.fastq.gz	Fastqsanger.gz
	SRR25180500_2.fastq.gz	Fastqsanger.gz
	SRR25180501_1.fastq.gz	Fastqsanger.gz
	SRR25180501_2.fastq.gz	Fastqsanger.gz
	SRR25180502_1.fastq.gz	Fastqsanger.gz

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Innate-like T cell subset commitment in the murine thymus is independent of TCR characteristics and occurs during proliferation

Project description:we compare the TCR repertoires of MAIT1 and MAIT17 cells from the mouse thymus using 5’ scRNAseq and scTCRseq of MR1:5-OP-RU tetramer positive thymocytes. A thorough analysis of TCR features between MAIT sub-populations did not show any difference between the repertoires of MAIT1 and MAIT17 subsets. Quantitative simulation of clonotype distributions of MAIT1 and MAIT17 cells allowed us to investigate the role of TCR characteristics in MAIT fate choice, and to pinpoint the stage at which lineage commitment occurs. Our results indicate that the TCR characteristics are not instructive in MAIT lineage choice and that MAIT1/17 commitment takes place during MAIT cell proliferation in the thymus. Finally, we performed analogous analysis of a published scRNA-seq and scTCR-seq dataset of iNKT from mouse thymus and demonstrated that our conclusions are also relevant for iNKT1 vs iNKT17 fate commitment.

2024-04-10 | GSE236666 | GEO

Innate-like T cell subset commitment in the murine thymus is independent of TCR characteristics and occurs during proliferation.

Project description:How T-cell receptor (TCR) characteristics determine subset commitment during T-cell development is still unclear. Here, we addressed this question for innate-like T cells, mucosal-associated invariant T (MAIT) cells, and invariant natural killer T (iNKT) cells. MAIT and iNKT cells have similar developmental paths, leading in mice to two effector subsets, cytotoxic (MAIT1/iNKT1) and IL17-secreting (MAIT17/iNKT17). For iNKT1 vs iNKT17 fate choice, an instructive role for TCR affinity was proposed but recent data argue against this model. Herein, we examined TCR role in MAIT and iNKT subset commitment through scRNAseq and TCR repertoire analysis. In our dataset of thymic MAIT cells, we found pairs of T-cell clones with identical amino acid TCR sequences originating from distinct precursors, one of which committed to MAIT1 and the other to MAIT17 fates. Quantitative in silico simulations indicated that the number of such cases is best explained by lineage choice being independent of TCR characteristics. Comparison of TCR features of MAIT1 and MAIT17 clonotypes demonstrated that the subsets cannot be distinguished based on TCR sequence. To pinpoint the developmental stage associated with MAIT sublineage choice, we demonstrated that proliferation takes place both before and after MAIT fate commitment. Altogether, we propose a model of MAIT cell development in which noncommitted, intermediate-stage MAIT cells undergo a first round of proliferation, followed by TCR characteristics-independent commitment to MAIT1 or MAIT17 lineage, followed by an additional round of proliferation. Reanalyzing a published iNKT TCR dataset, we showed that this model is also relevant for iNKT cell development.

| S-EPMC10998581 | biostudies-literature

Single-cell immune profiling reveals thymus-seeding populations, T cell commitment, and multi-lineage development in the human thymus

Project description:Development of T lymphocytes in the thymus has been widely studied in mice, but our insights into human T cell development are scarce. Using a combination of single-cell techniques and functional assays, we report deep immune profiling of human T cell development, with a focus on the initial development stages of pre-lineage commitment. We identified three thymus-seeding progenitor populations that also have a counterpart in the bone marrow. We found that the human thymus physiologically supports development of monocytes, DCs, NK cells, and limited development of B lymphocytes. These insights are important to monitor and guide regenerative therapies after hematopoietic stem cell transplantation.

2022-08-01 | GSE195812 | GEO

Single-cell immune profiling reveals thymus-seeding populations, T cell commitment, and multi-lineage development in the human thymus

Project description:Single-cell immune profiling reveals thymus-seeding populations, T cell commitment, and multi-lineage development in the human thymus

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Modulation of TCR signalling components occurs prior to positive selection and lineage commitment in iNKT cells.

Project description:iNKT cells play a critical role in controlling the strength and character of adaptive and innate immune responses. Their unique functional characteristics are induced by a transcriptional program initiated by positive selection mediated by CD1d expressed by CD4+CD8+ (double positive, DP) thymocytes. Here, using a novel Vα14 TCR transgenic strain bearing greatly expanded numbers of CD24hiCD44loNKT cells, we examined transcriptional events in four immature thymic iNKT cell subsets. A transcriptional regulatory network approach identified transcriptional changes in proximal components of the TCR signalling cascade in DP NKT cells. Subsequently, positive and negative selection, and lineage commitment, occurred at the transition from DP NKT to CD4 NKT. Thus, this study introduces previously unrecognised steps in early NKT cell development, and separates the events associated with modulation of the T cell signalling cascade prior to changes associated with positive selection and lineage commitment.

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rhesus monkey thymus proteomics of FNC

Project description:Thymus is the important immune organ, responsible for T cell development and differentiation.We conduct rhesus monkey thymus proteomics of FNC.

2024-08-10 | PXD050624 | Pride

Single cell RNA-seq of metabolite specific T-cells (MR1-restricted) from adult mouse thymus

Project description:Mucosal-Associated Invariant T cells (MAIT cells) have a unique specificity for the microbial metabolite 5-OP-RU presented by the non-classical presentation molecule MR1. Upon activation, they release cytotoxic mediators and engage an antimicrobial activity. As a subset of T lymphocytes, MAIT development occurs in the thymus where they acquire their effector phenotype under the control of the key transcription factor ZBTB16. This particular maturation process is in contrast with conventional T cells that egress the thymus with a naive phenotype before populating the secondary lymphoid organs, and the molecular events driving the MAIT lineage decision are poorly known. In the present work, we evaluated the transcriptional events and the role of the slam-SAP pathway on the lineage decision of MR1-restricted T cells by single cell RNAseq. MAIT cells undergoing positive selection were FACS-sorted with a MR1:5-OP-RU labeled tetramer, from thymus of wild-type and sapKO mice. Their transcriptomes were captured using a 10x chromium system.

2019-07-01 | E-MTAB-7704 | biostudies-arrayexpress

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Ormyrus thymus

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