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Bcl11b binding and transcriptome analysis of Bcl11b-deficient MAIT cells at steady state and infection

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus Homo sapiens

PROVIDER: GSE145779 | GEO | 2021/03/22

REPOSITORIES: GEO

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Transcriptome analysis of Bcl11b-deficient MAIT cells at steady state and infection

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 | GSE145778 | GEO

Bcl11b binding and transcriptome analysis of Bcl11b-deficient MAIT cells at steady state and infection

Project description:Bcl11b binding and transcriptome analysis of Bcl11b-deficient MAIT cells at steady state and infection

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Transcriptome analysis of Bcl11b-deficient MAIT cells at steady state and infection

Project description:Transcriptome analysis of Bcl11b-deficient MAIT cells at steady state and infection

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Transcriptome analysis of Bcl11b-deficient regulatory T cells at steady state

Project description:T regulatory (Treg) cells have been studied in depth since their discovery for their potential use in therapies of autoimmune diseases. Treg cells have a suppression program that includes surface molecules CD25 (IL2R), cytotoxic T-lymphocyte associated protein 4 (CTLA4), and glucocorticoid-induced TNFR family (GITR) to limit aberrant and excessive inflammatory immune responses. We have shown that Bcl11b can bind to the CNS2 region in Foxp3 as well as the gene loci of those essential surface molecules for Treg suppression. Furthermore, we have identified a subset of Foxp3-independent genes in Treg cells directly regulated by Bcl11b binding. Bcl11b also directly represses expression of innate molecules such as transcription factors PU.1 and ID2 in Treg cells. Finally, we have also shown that removal of Bcl11b accelerates apoptosis in Treg cells as cleaved caspase 3 levels were significantly elevated in Bcl11b KO Treg cells when compared with WT Treg cells.

2019-08-07 | GSE120874 | GEO

Transcriptome analysis of Bcl11b-deficient regulatory T cells at steady state

Project description:Transcriptome analysis of Bcl11b-deficient regulatory T cells at steady state

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Mapping Bcl11b binding in human MAIT cells

2021-03-22 | GSE145776 | GEO

Human MAIT cells exit peripheral tissues and recirculate via lymph in steady state conditions.

Project description:Mucosal-associated invariant T cells (MAIT cells) recognize bacterial metabolites as antigen and are found in blood and tissues, where they are poised to contribute to barrier immunity. Recent data demonstrate that MAIT cells located in mucosal barrier tissues are functionally distinct from their blood counterparts, but the relationship and circulation of MAIT cells between blood and different tissue compartments remains poorly understood. Previous studies raised the possibility that MAIT cells do not leave tissue and may either be retained or undergo apoptosis. To directly address if human MAIT cells exit tissues, we collected human donor-matched thoracic duct lymph and blood and analyzed MAIT cell phenotype, transcriptome, and T cell receptor (TCR) diversity by flow cytometry and RNA sequencing. We found that MAIT cells were present in the lymph, despite being largely CCR7- in the blood, thus indicating that MAIT cells in the lymph migrated from tissues and were capable of exiting tissues to recirculate. Importantly, MAIT cells in the lymph and blood had highly overlapping clonotype usage but distinct transcriptome signatures, indicative of differential activation states.

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Genome wide mapping in regulatory T cells at steady state

Project description:This SuperSeries is composed of the SubSeries listed below.

2019-08-07 | GSE120875 | GEO

Mapping Bcl11b binding in human MAIT cells

Project description:Mapping Bcl11b binding in human MAIT cells

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BCL11B

Project description:This SuperSeries is composed of the SubSeries listed below.

2017-03-06 | GSE84678 | GEO