Mouse iNKT cell: Wild type Vs Bcl11b deficient
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE73679 | GEO | 2016/08/10
SECONDARY ACCESSION(S): PRJNA297634
REPOSITORIES: GEO
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Project description:Transcriptional profiling of mouse iNKT cells comparing wild type and Bcl11b deficient cell. The mice were treated with 4 μg of α-galactosylceramide. Goal was to determine the effects of transcription factor Bcl11b removal in iNKT cells. Intraperitoneal treatment with 4 μg of α-Galactosylceramide. Two pair of wild type (BCL11b F/F Vα14 transgenic) and Knock out (BCL11b F/F PLZF-Cre Vα14 transgenic)) mice were treated. Lymphocytes from spleen and liver were enriched and stain with PBS-57 Loaded CD1d tetramer. Pure iNKT cells were collected through cell sorter.
2016-08-10 | E-GEOD-73679 | biostudies-arrayexpress
Project description:Regulatory B cells (Breg) express high levels of CD1d that presents lipid antigens to invariant natural killer T (iNKT) cells. The function of CD1d in Breg biology and iNKT cell activity during inflammation remains unclear. Here we show, using chimeric mice, cell depletion and adoptive cell transfer, that CD1d-lipid presentation by Bregs induces iNKT cells to secret IFN-γ to contribute, partially, to the down-regulation of T helper (Th)1 and Th17 adaptive immune responses for ameliorating experimental arthritis. Mice lacking CD1d-expressing B cells develop exacerbated diseases compared to wild-type mice, and fail to respond to α-galactosylceramide treatment. Absence of lipid presentation by B cells causes altered activation of iNKT cells, with disruption of regulatory pathways including those involved in metabolism and cytokine responses. Thus, we identify an IL-10-independent mechanism by which Bregs restrain excessive inflammation via lipid presentation.
2018-01-25 | E-MTAB-6381 | biostudies-arrayexpress
Project description:expression profile in Bcl11b-deficient Treg cells versus wild type Treg cells Treg cells sorted from Bcl11bF/F/Cd4Cre/Foxp3-GFP+ mice and wild type Foxp3-GFP+ mice Treg cells sorted from Bcl11bF/F/Foxp3Cre mice and wild type mice RNA extracted from sorted Bcl11b-deficient Foxp3-GFP Treg cells form Bcl11bF/F/Cd4Cre/Foxp3-GFP+ mice and wild type Foxp3-GFP Treg cells; expression profile by microarray analysis RNA extracted from sorted Bcl11b-deficient Treg cells form Bcl11bF/F/Foxp3Cre mice and wild type Treg cells; expression profile by microarray analysis
2011-08-27 | E-GEOD-30523 | biostudies-arrayexpress
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
Project description:Development of T cells is controlled by the signal strength of the TCR. The scaffold protein Kinase D-interacting substrate of 220 kDa (Kidins220) binds to the TCR; however, its role in T cell development was unknown. Here, we show that T cell-specific Kidins220 knock-out (T-KO) mice have strongly reduced invariant natural killer T (iNKT) cell numbers and modest decreases in conventional T cells. Enhanced apoptosis due to increased TCR signaling in T-KO iNKT thymocytes of developmental stage 2 and 3 shows that Kidins220 downregulates TCR signaling at these stages. scRNAseq indicated that the transcription factor Aiolos is downregulated in Kidins220-deficient iNKT cells. Analysis of an Aiolos KO demonstrated that Aiolos is a downstream effector of Kidins220 during iNKT cell development. In the periphery, T-KO iNKT cells show reduced TCR signaling upon stimulation with α-galactosylceramide, suggesting that Kidins220 promotes TCR signaling in peripheral iNKT cells. Thus, Kidins220 reduces or promotes signaling dependent on the iNKT cell developmental stage.
2024-03-11 | GSE253196 | GEO
Project description:Invariant NKT (iNKT) cells comprise a heterogeneous group of terminally differentiated, non-circulating, tissue-resident T-lymphocytes that recognize glycolipids, including alpha-galactosylceramide (aGalCer), in the context of CD1d. Here, we show that murine and human liver-resident aGalCer/CD1d-binding iNKTs correspond to a novel Zbtb16+/Tbx21+/Gata3+/Maflow/Rorc– subset that exhibits profound plasticity. Repetitive encounters of these cells with intravenously-delivered aGalCer/CD1d-coated nanoparticles (NPs) trigger their differentiation into immunoregulatory, IL-10/IL-21-producing, Mafhigh cells expressing a T-regulatory type 1 (TR1)-like transcriptional signature.
2022-04-22 | GSE168488 | GEO
Project description:We performed RNA sequencing of primary human iNKT cell lines pulsed with Fn or αGalCer, the prototype agonist of iNKT cells. Fn-primed iNKT cells showed an enriched neutrophil chemotaxis gene signature, including the chemokine C-X-C and C-C motif ligand family genes. αGalCer-primed iNKT cells presented an IFNγ/cytotoxic-related gene signature.
2023-04-16 | E-MTAB-12281 | biostudies-arrayexpress
Project description:B-cell leukemia 11b (BCL11B) is a transcription factor known as an essential regulator of T lymphocytes and neuronal development during embryogenesis. A genome-wide association study (GWAS) showed that a gene desert region downstream of BCL11B, known to function as a BCL11B enhancer, harbors single nucleotide polymorphisms (SNPs) associated with increased arterial stiffness. However, a role for BCL11B in the adult cardiovascular system is unknown. Based on these human findings, we sought to examine the relation between BCL11B and arterial function. Here we report that BCL11B is expressed in the vascular smooth muscle (VSM) where it regulates vascular stiffness. RNA sequencing of aortas from WT and Bcl11b null mice (BSMKO) identified the cyclic guanosine monophosphate (cGMP)-protein kinase G (PKG) as the most significant differentially regulated signaling pathway in BSMKO compared to WT mice. BSMKO aortas showed decreased levels of PKG1, increased levels of Ca++-calmodulin-dependent serine/threonine phosphatase calcineurin (PP2B) and their common phosphorylation target, vasodilator-stimulated phosphoprotein (pVASPS239), a regulator of cytoskeletal actin rearrangements. Decreased pVASPS239 in BSMKO aortas was associated with increased actin polymerization (F/G actin ratio). Functionally, aortic force, stress, wall tension and stiffness, measured ex vivo in organ baths, were increased in BSMKO aortas, and BSMKO mice had increased pulse wave velocity, the in vivo index of arterial stiffness. Despite having no effect on blood pressure or microalbuminuria, increased arterial stiffness in BSMKO mice was associated with increased incidence of cerebral microbleeds compared to age-matched WT littermates. In conclusion, we have identified VSM BCL11B as a crucial regulator of aortic smooth muscle function and a potential therapeutic target for vascular stiffness.
2021-12-01 | GSE163551 | GEO
Project description:Epigenetic landscapes can provide insight into regulation of gene expression and cellular diversity. Here, we examined the transcriptional and epigenetic profiles of seven human blood NK cell populations, including adaptive NK cells. The BCL11B gene, encoding a transcription factor (TF) essential for T cell development and function, was the most extensively regulated, with expression increasing throughout NK cell differentiation. Several Bcl11b-regulated genes associated with T cell-signaling were specifically expressed in adaptive NK cell subsets. Regulatory networks revealed reciprocal regulation at distinct stages of NK cell differentiation, with Bcl11b repressing RUNX2 and ZBTB16 in canonical and adaptive NK cells, respectively. A critical role for Bcl11b in driving NK cell differentiation was corroborated in BCL11B mutated patients and by ectopic Bcl11b expression. Moreover, Bcl11b was required for adaptive NK cell responses in a murine CMV model, supporting expansion of these cells. Together, we define the TF regulatory circuitry of human NK cells and uncover a critical role for Bcl11b in promoting NK cell differentiation and function.
2021-05-28 | GSE162472 | GEO
