MAIT cell plasticity enables functional adaption that drives anti-bacterial immune protection
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE274087 | GEO | 2024/12/06
REPOSITORIES: GEO
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Project description:MAIT cell plasticity enables functional adaption that drives anti-bacterial immune protection
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Project description:In mice, contrary to conventional T cells, MAIT cells acquire a memory phenotype in the thymus in relation with Zbtb16 expression (Savage et al., 2008 ; Koay et al., 2016). To define phenotypic transcriptional signatures of MAIT subsets in the thymus, we analyzed by microarray the transcriptome of MAIT1 (MR1tet+RORgt+) and MAIT17 (MR1tet+RORgt+) as compared to conventional mature (TCRb+CD24lo) CD4+ and CD8+ single positive cells.
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Project description:Glioblastoma (GBM) is the most aggressive primary brain cancer in adults and remains incurable. We used multi-omics and flow cytometry methods to investigate the role of mucosal-associated invariant T (MAIT) cells in GBM. In bulk RNA sequencing data analysis of GBM tissues, MAIT cell gene signature significantly correlated with poor patient survival. A scRNA-seq of CD45+ cells from 23 GBM tissue samples showed a diverse immune population in the GBM tumor microenvironment. Of the 23 GBM tissue samples analyzed, 15 (65.2%) were positive for MAIT cells. MAIT cells clustered with cell populations expressing a high level of transcription factor gene RORC, suggesting the enrichment of MAIT17 subset. The MAIT cell signature significantly correlated with the activity of tumor-associated neutrophils (TANs) and myeloid-derived suppressor cells (MDSCs). Multiple immune suppressive genes known to be used by TANs/MDSCs were upregulated in MAIT-positive tumors. Spatial imaging analysis of GBM tissues showed that all specimens were positive for both MAIT cells and TANs and localized enrichment of TANs. These findings highlight the MAIT-TAN/MDSC axis as a novel therapeutic target to modulate GBM’s immunosuppressive tumor microenvironment.
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Project description:Mucosal-associated invariant T (MAIT) cells are a subpopulation of T lymphocytes that respond to microbial metabolites. We performed single-cell RNA sequencing and metabolic analyses in MAIT cell subsets in thymus and peripheral tissues from mice and humans to define the heterogeneity and developmental path of these innate-like lymphocytes. We show that the predominant mouse subset, which produces IL-17 (MAIT17), and the subset that produces IFN (MAIT1), have greatly different transcriptomes and metabolic states in the thymus and periphery. A subset has a transcriptome similar to circulating lymphocytes, and in mice these are found in recent thymic emigrants, suggesting partially mature cells emigrate from the thymus. Human MAIT cells are predominantly MAIT1 cells, but have a different metabolism from naïve CD8 T cells with increased fatty acid uptake and storage. Although mouse and human subsets are similar in thymus, in the periphery they are divergent, likely reflecting environmental and genetic differences.
2023-11-13 | GSE189484 | GEO
Project description:Mucosal-associated invariant T (MAIT) cells are a subpopulation of T lymphocytes that respond to microbial metabolites. We performed single-cell RNA sequencing and metabolic analyses in MAIT cell subsets in thymus and peripheral tissues from mice and humans to define the heterogeneity and developmental path of these innate-like lymphocytes. We show that the predominant mouse subset, which produces IL-17 (MAIT17), and the subset that produces IFN (MAIT1), have greatly different transcriptomes and metabolic states in the thymus and periphery. A subset has a transcriptome similar to circulating lymphocytes, and in mice these are found in recent thymic emigrants, suggesting partially mature cells emigrate from the thymus. Human MAIT cells are predominantly MAIT1 cells, but have a different metabolism from naïve CD8 T cells with increased fatty acid uptake and storage. Although mouse and human subsets are similar in thymus, in the periphery they are divergent, likely reflecting environmental and genetic differences.
2023-11-13 | GSE189483 | GEO
Project description:At variance with what is observed in mice, no distinct MAIT1 or MAIT17 subsets exist in human blood, as all MAIT cells express a variety of transcription factors such as Rorgt, Tbet, Eomes and Helios. However, they are also found in tissues in which they have specific effector functions. To determine these tissue programs, we analyzed the transcription pattern of MAIT cells as compared to mainstream memory (CD45RA-CD27+) CD4+ and CD8+ T cells from human blood and liver. The paired samples of blood and liver cells were obtained from patients operated for metastatic uveal melanoma (liver samples from a “healthy” liver fragment), and from the blood of healthy controls.
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Project description:Mucosal associated invariant T (MAIT) cells, already differentiated and located at mucosal sites, are critical in the body’s first wave of defenses against invading pathogens. Bcl11b KO MAIT cells fail to be maintained both in the thymus and peripheral organs. Furthermore, MAIT cells fail to fully develop in the thymus without Bcl11b, failing to upregulate RORγt, and that phenotype remains in the lungs and livers of these mice. Bcl11b deletion in MAIT cells causes dramatic shifts in the activation and TH17 programs, due to the binding of Bcl11b in many of those genes, which we have seen in the human MAIT cells. MAIT cells rely on PLZF and RORγt for their development and function, while also heavily relying on Bcl11b. These data show the key interplay of Bcl11b with PLZF and RORγt in a T cell leading to its development and necessary function to protect the body against diseases.
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Project description:Mucosal associated invariant T (MAIT) cells, already differentiated and located at mucosal sites, are critical in the body’s first wave of defenses against invading pathogens. Bcl11b KO MAIT cells fail to be maintained both in the thymus and peripheral organs. Furthermore, MAIT cells fail to fully develop in the thymus without Bcl11b, failing to upregulate RORγt, and that phenotype remains in the lungs and livers of these mice. Bcl11b deletion in MAIT cells causes dramatic shifts in the activation and TH17 programs, due to the binding of Bcl11b in many of those genes, which we have seen in the human MAIT cells. MAIT cells rely on PLZF and RORγt for their development and function, while also heavily relying on Bcl11b. These data show the key interplay of Bcl11b with PLZF and RORγt in a T cell leading to its development and necessary function to protect the body against diseases.
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Project description:Mucosal-Associated Invariant T (MAIT) cells are an innate-like subset of alpha/beta-T cells expressing semi-invariant TCRs that recognize conserved vitamin B2 metabolite-based antigens from microbes, thus contributing to protection against several bacterial pathogens. To investigate the transcriptomic changes induced during systemic Francisella tularensis infection, liver MAIT cells were recovered from naïve mice and mice at days 13 and 48 post infection.
2021-05-19 | E-MTAB-10239 | biostudies-arrayexpress
Project description:A recently identified unconventional T cell population known as mucosal-associated invariant T (MAIT) cells are characterized by the expression of semi-invariant T cell receptor (TCR) with a canonical TRAV1-2/TRAJ33 (Vα7.2/Jα33). These evolutionary conserved, innate-like T cells recognize vitamin B metabolites, derived from some bacteria and fungi. Due to their presence not only in the T cell repertoire of mucosal surfaces but also in peripheral blood and liver, and their significant involvement in a wide range of diseases, in-depth characterization of human MAIT cells is a timely requirement. Studies that examined the transcriptome, immunoproteome, and whole-cell proteome characterized the role of cytotoxic molecules and cytokines in effector functions of MAIT cells and their relationship with some other immune cell subsets. As MAIT cells are classified under the CD3+ T cell compartment and the majority express surface receptor CD8, identifying their proteomic relationship with CD3+ and CD8+ T cells is pivotal. Thus, a high-resolution dataset was generated using the cell populations sorted from peripheral blood mononuclear cells of three healthy volunteers to describe the whole cell proteomes of MAIT, CD3+, and CD8+ T cells. Trypsin-digested peptide samples obtained from the methanol co-precipitation method were analyzed using an Orbitrap FusionTM TribridTM mass spectrometer (Thermo Fisher Scientific, USA) inline coupled to nanoACQUITY ultra-performance liquid chromatography system (Waters, USA) to acquire data-dependent shotgun proteomic data (DDA-MS) for label-free quantification. Analysis of raw DDA-MS data using MaxQuant software and maxLFQ identified and quantified 4,442 protein groups at a 1% false discovery rate. Further analysis identified 3,680 proteins which were detected with a single UniProt accession and a minimum of 2 unique or razor peptides. Thus this proteomic dataset can be used as a reference proteome for future studies on human MAIT cells.
2024-08-04 | PXD052574 | Pride