Multiomic analysis reveals decidual-specific transcriptional programing of MAIT cells
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PROVIDER: PRJNA760547 | ENA |
REPOSITORIES: ENA
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Project description:Problem: Mucosal-Associated Invariant T (MAIT) cells have been recently identified at the maternal-fetal interface. However, transcriptional programming of decidual MAIT cells in pregnancy remains poorly understood. Method of Study: We employed a multiomic approach to address this question. Mononuclear cells from the decidua basalis and parietalis, and control PBMCs, were analyzed via flow cytometry to investigate MAIT cells in the decidua and assess their transcription factor expression. In a separate study, both decidual and matched peripheral MAIT cells were analyzed using Cellular Indexing of Transcriptomes and Epitopes by Sequencing (CITE-seq) coupled with gene expression analysis. Lastly, decidual MAIT cells were stimulated with E. coli and expression of MR1 by antigen presenting cells was measured to evaluate decidual MAIT cell function. Results: First, we identified MAIT cells in both the decidua basalis and parietalis. CITE-seq, coupled with scRNAseq gene expression analysis, highlighted transcriptional programming differences between decidual and matched peripheral MAIT cells at a single cell resolution. Transcription factor expression analysis further highlighted transcriptional differences between decidual MAIT cells and non-matched peripheral MAIT cells. Functionally, MAIT cells are skewed towards IFNg and TNFa production upon stimulation, with E. coli leading to IFNg production. Lastly, we demonstrate that MR1, the antigen presenting molecule restricting MAIT cells, is expressed by decidual APCs. Conclusion: MAIT cells are present in the decidua basalis and obtain a unique gene expression profile. The presence of MR1 on APCs coupled with in vitro activation by E. coli suggests that MAIT cells might be involved in tissue-repair mechanisms at the maternal-fetal interface.
2021-09-07 | GSE183421 | GEO
Project description:ProblemMucosal-Associated Invariant T (MAIT) cells have been recently identified at the maternal-fetal interface. However, transcriptional programming of decidual MAIT cells in pregnancy remains poorly understood.Method of studyWe employed a multiomic approach to address this question. Mononuclear cells from the decidua basalis and parietalis, and control PBMCs, were analyzed via flow cytometry to investigate MAIT cells in the decidua and assess their transcription factor expression. In a separate study, both decidual and matched peripheral MAIT cells were analyzed using Cellular Indexing of Transcriptomes and Epitopes by Sequencing (CITE-seq) coupled with gene expression analysis. Lastly, decidual MAIT cells were stimulated with E.coli and expression of MR1 by antigen presenting cells was measured to evaluate decidual MAIT cell function.ResultsFirst, we identified MAIT cells in both the decidua basalis and parietalis. CITE-seq, coupled with scRNA-seq gene expression analysis, highlighted transcriptional programming differences between decidual and matched peripheral MAIT cells at a single cell resolution. Transcription factor expression analysis further highlighted transcriptional differences between decidual MAIT cells and non-matched peripheral MAIT cells. Functionally, MAIT cells are skewed towards IFNγ and TNFα production upon stimulation, with E.coli leading to IFNγ production. Lastly, we demonstrate that MR1, the antigen presenting molecule restricting MAIT cells, is expressed by decidual APCs.ConclusionMAIT cells are present in the decidua basalis and obtain a unique gene expression profile. The presence of MR1 on APCs coupled with in vitro activation by E.coli suggests that MAIT cells might be involved in tissue-repair mechanisms at the maternal-fetal interface.
| S-EPMC8720468 | biostudies-literature
Project description:To show the similarity among MAIT-iPSCs, hiPSCs and hESCs and the gradual change of global gene expression of reMAIT cells along with differentiation, this experiment was designed. MAIT cells, MAIT-iPSCs, hiPSCs, hESCs, MAIT cells, and reMAIT cells at the several differerent stages of differentiation were collected. Then, they were applied in this experiment.
2013-03-21 | E-GEOD-44559 | biostudies-arrayexpress
Project description:MAIT cells (MAITs) represent an abundant T lymphocyte subset with unique specificity for microbial metabolites presented by the MHC-1b molecule, MR1. MAIT conservation along evolution indicates important, non-redundant functions, but their low frequency in mice has hampered their detailed characterization. Here, we performed a transcriptomic analysis of murine MAITs in comparison with NKT subsets and with mainstream T cells in spleen and peripheral organs of B6-MAIT/CAST mice expressing a Rorc-GFP transgene. MAIT and NKT cells have been FACS-sorted after tetramer staining (MR1:5-OP-RU Tet+ for MAIT, CD1d:PBS57Tet+ for NKT), and 1/17 subsetting based on the expression of Rorc.
2018-12-03 | E-MTAB-7133 | biostudies-arrayexpress
Project description:A Toxoplasma gondii infection during pregnancy can result in spontaneous abortion, preterm labor, or congenital fetal defects. The decidual immune system plays a critical role in regulating the immune micro-environment and in the induction of immune tolerance. To better understand the factors that mediate the decidual immune response associated with the T. gondii infection, a large-scale study employing TMT proteomics was conducted to characterize the differential decidual immune proteomes from infected and uninfected human decidual immune cells samples. The decidual immune cells from 105 human voluntary abortion tissues were purified, and of the 5510 unique proteins identified, 181 proteins were found to be differentially abundant (>1.2-fold cutoff, P＜0.05) in the T. gondii-infected decidual immune cells. 11 proteins of 181 differentially expressed proteins associated with trophoblast invasion, placental development, intrauterine fetal growth, and immune tolerance were verified using a quantitative real-time polymerase chain reaction and western blotting. This systematic research identified a broad range of immune factors in human decidual immune cells, shedding a new insight into the decidual immune molecular mechanism for abnormal pregnancy outcomes associated with T. gondii infection.
2018-07-27 | PXD008448 | Pride
Project description:Obesity underpins the development of numerous chronic diseases such as type II diabetes mellitus. It is well established that obesity negatively alters immune cell frequencies and functions. Mucosal Associated Invariant T (MAIT) cells are a population of innate T cells, which we have previously reported are dysregulated in obesity, with altered circulating and adipose tissue frequencies and a reduction in their IFN-gamma production, which is a critical effector function of MAIT cells in host defence. Hence there is increased urgency to characterise the key molecular mechanisms that drive MAIT cell effector functions, and to identify those which are impaired in the obesity setting. In this study, we found that MAIT cells significantly upregulate their rates of glycolysis upon activation in an mTORC1 dependent manner and this is essential for MAIT cell IFN-g production. Furthermore, we show that mTORC1 activation is dependent on amino acid transport via SLC7A5. In obese patients, using RNA sequencing, Seahorse analysis and a series of in vitro experiments, we demonstrate that MAIT cells isolated from obese adults display defective glycolytic metabolism, mTORC1 signalling and SLC7A5 amino acid transport. Collectively our data details the intrinsic metabolic pathways controlling MAIT cell cytokine production and highlights mTORC1 as an important metabolic regulator that is impaired in obesity, leading to altered MAIT cell responses. We report on MAIT cells isolated from lean and obese adults
2019-04-16 | GSE126169 | GEO
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.
2019-07-01 | E-MTAB-7702 | biostudies-arrayexpress
Project description:Mucosal-associated invariant T (MAIT) cells are innate-like lymphocytes that recognize microbial vitamin B metabolites and have emerging roles in infectious disease, autoimmunity, and cancer. Although MAIT cells are identified by a semi-invariant T cell receptor, their phenotypic and functional heterogeneity is not well understood. Here we present an integrated single cell transcriptomic analysis of over 76,000 human MAIT cells during acute and chronic antigen-specific activation with the MR1 ligand 5-OP-RU and non-specific TCR stimulation. We show that MAIT cells span a broad range of homeostatic, effector, helper, tissue-infiltrating, regulatory, and exhausted phenotypes, with distinct gene expression programs associated with CD4+ or CD8+ co-expression. During acute activation, MAIT cells rapidly adopt a cytotoxic phenotype characterized by high expression of GZMB, IFNG and TNF. In contrast, chronic stimulation induces heterogeneous states defined by proliferation, cytotoxicity, immune modulation, and exhaustion. We further demonstrate a FOXP3 expressing MAIT cell subset that phenotypically resembles conventional regulatory T cells. Moreover, scRNAseq-defined MAIT cell subpopulations were also detected in individuals recently exposed to Mycobacterium tuberculosis, confirming their presence during human infection. Our study provides the first comprehensive atlas of human MAIT cells in activation conditions and defines substantial functional heterogeneity, suggesting complex roles in health and disease.
2021-08-19 | GSE182239 | GEO
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.
2021-03-22 | GSE145777 | GEO