SLAM/SAP signaling regulates discrete γδ T cell developmental checkpoints and shapes the innate-like γδ TCR repertoire
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1090116 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR28400200_1.fastq.gz | Fastqsanger.gz | |||
| SRR28400200_2.fastq.gz | Fastqsanger.gz | |||
| SRR28400201_1.fastq.gz | Fastqsanger.gz | |||
| SRR28400201_2.fastq.gz | Fastqsanger.gz | |||
| SRR28400202_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 24 |
Similar Datasets
Project description:During thymic development, most γδ T cells acquire innate-like characteristics that are critical for their function in tumor surveillance, infectious disease, and tissue repair. The mechanisms, however, that regulate γδ T cell developmental programming remain unclear. Recently, we demonstrated that the SLAM-SAP signaling pathway regulates the development and function of multiple innate-like γδ T cell subsets. Here, we used a single-cell proteogenomics approach to identify SAP-dependent developmental checkpoints and to define the SAP-dependent γδ TCR repertoire. SAP deficiency resulted in both a significant loss of an immatureGzma+Blk+Etv5+Tox2+γδT17 precursor population, and a significant increase inCd4+Cd8+Rorc+Ptcra+Rag1+thymic γδ T cells. SAP-dependent diversion of embryonic day 17 thymic γδ T cell clonotypes into the αβ T cell developmental pathway was associated with a decreased frequency of mature clonotypes in neonatal thymus, and an altered γδ TCR repertoire in the periphery. Finally, we identify TRGV4/TRAV13-4(DV7)-expressing T cells as a novel, SAP-dependent Vγ4 γδT1 subset. Together, the data suggest that SAP-dependent γδ/αβ T cell lineage commitment regulates γδ T cell developmental programming and shapes the γδ TCR repertoire.
2024-07-08 | GSE262064 | GEO
Project description:During thymic development, most γδ T cells acquire innate-like characteristics that are critical for their function in tumor surveillance, infectious disease, and tissue repair. The mechanisms, however, that regulate γδ T cell developmental programming remain unclear. Recently, we demonstrated that the SLAM-SAP signaling pathway regulates the development and function of multiple innate-like γδ T cell subsets. Here, we used a single-cell proteogenomics approach to identify SAP-dependent developmental checkpoints and to define the SAP-dependent γδ TCR repertoire. SAP deficiency resulted in both a significant loss of an immature Gzma + Blk + Etv5 + Tox2 + γδT17 precursor population, and a significant increase in Cd4 + Cd8+ Rorc + Ptcra + Rag1 + thymic γδ T cells. SAP-dependent diversion of embryonic day 17 thymic γδ T cell clonotypes into the αβ T cell developmental pathway was associated with a decreased frequency of mature clonotypes in neonatal thymus, and an altered γδ TCR repertoire in the periphery. Finally, we identify TRGV4/TRAV13-4(DV7)-expressing T cells as a novel, SAP-dependent Vγ4 γδT1 subset. Together, the data suggest that SAP-dependent γδ/αβ T cell lineage commitment regulates γδ T cell developmental programming and shapes the γδ TCR repertoire.
| S-EPMC10802474 | biostudies-literature
Project description:During thymic development, most γδ T cells acquire innate-like characteristics that are critical for their function in tumor surveillance, infectious disease, and tissue repair. The mechanisms, however, that regulate γδ T cell developmental programming remain unclear. Recently, we demonstrated that the SLAM/SAP signaling pathway regulates the development and function of multiple innate-like γδ T cell subsets. Here, we used a single-cell proteogenomics approach to identify SAP-dependent developmental checkpoints and to define the SAP-dependent γδ TCR repertoire in mice. SAP deficiency resulted in both a significant loss of an immature Gzma+Blk+Etv5+Tox2+ γδT17 precursor population and a significant increase in Cd4+Cd8+Rorc+Ptcra+Rag1+ thymic γδ T cells. SAP-dependent diversion of embryonic day 17 thymic γδ T cell clonotypes into the αβ T cell developmental pathway was associated with a decreased frequency of mature clonotypes in neonatal thymus, and an altered γδ TCR repertoire in the periphery. Finally, we identify TRGV4/TRAV13-4(DV7)-expressing T cells as a novel, SAP-dependent Vγ4 γδT1 subset. Together, the data support a model in which SAP-dependent γδ/αβ T cell lineage commitment regulates γδ T cell developmental programming and shapes the γδ TCR repertoire.
| S-EPMC11630817 | biostudies-literature
Project description:A common genetic variant in the gene encoding the protein tyrosine phosphatase nonreceptor type 22 (PTPN22 C1858T) has been linked to a wide range of autoimmune disorders. Although a B cell-intrinsic role in promoting disease has been reported, the mechanism(s) through which this variant functions to alter the preimmune B cell repertoire remains unknown. Using a series of polyclonal and transgenic self-reactive models harboring the analogous mutation in murine Ptpn22, we show evidence for enhanced BCR, B cell-activating factor receptor, and CD40 coreceptor programs, leading to broadly enhanced positive selection of B cells at two discrete checkpoints in the bone marrow and spleen. We further identified a bias for selection of B cells into the follicular mature versus marginal zone B cell compartment. Using a biomarker to track a self-reactive H chain in peripheral blood, we found evidence of similarly enhanced positive selection in human carriers of the PTPN22 C1858T variant. Our combined data support a model whereby the risk variant augments the BCR and coreceptor programs throughout B cell development, promoting enrichment of self-reactive specificities into the follicular mature compartment and thereby likely increasing the risk for seeding of autoimmune B cell responses.
| S-EPMC6791366 | biostudies-literature
Project description:The mammalian gastrointestinal tract harbors thousands of bacterial species that include symbionts as well as potential pathogens. The immune responses that limit access of these bacteria to underlying tissue remain poorly defined. In this study, we used microarrays to uncover the transcriptional responses that occur in small intestinal γδ intraepithelial lymphocytes following bacterial challenge. γδ intraepithelial lymphocytes (γδ IEL) were isolated by flow cytometry from the small intestines of germ-free mice, or from age- and sex-matched conventionally-raised counterparts. We extracted RNAs from these purified γδ IEL for analysis on Affymetrix DNA microarrays. The mice were all >8 weeks in age, and each sample represents a pool of RNAs from 5-8 mice.
2011-04-06 | E-GEOD-28437 | biostudies-arrayexpress
Project description:RNA expression of unstimulated γδ-T cells,γδ-TCR-stimulated γδ-T cells, unstimulated αβ-TCR transduced γδ-T cells and αβ-TCR-stimulated αβ-TCR transduced γδ-T cells.
2023-09-07 | GSE216880 | GEO
Project description:Triple negative breast cancer (TNBC) lacks targeted therapy options. TNBC is enriched in breast cancer stem cells (BCSCs), which play a key role in metastasis, chemoresistance, relapse and mortality. γδ T cells hold great potential in immunotherapy against cancer, and might be an alternative to target TNBC. γδ T cells are commonly observed to infiltrate solid tumors and have an extensive repertoire of tumor sensing, recognizing stress-induced molecules and phosphoantigens (pAgs) on transformed cells. We show that patient derived triple negative BCSCs are efficiently recognized and killed by ex vivo expanded γδ T cells from healthy donors. Orthotopically xenografted BCSCs, however, were refractory to γδ T cell immunotherapy. Mechanistically, we unraveled concerted differentiation and immune escape: xenografted BCSCs lost stemness, expression of γδ T cell ligands, adhesion molecules and pAgs, thereby evading immune recognition by γδ T cells. Indeed, neither pro-migratory engineered γδ T cells, nor anti-PD 1 checkpoint blockade significantly prolonged overall survival of tumor-bearing mice. BCSC immune escape was independent of the immune pressure exerted by the γδ T cells, and could be pharmacologically reverted by Zoledronate or IFN-α treatment. These results pave the way for novel combinatorial immunotherapies for TNBC.
2023-07-20 | PXD039463 | Pride
Project description:The murine thymus produces discrete γδ T cell subsets making either IFN-γ or IL-17, but the role of the TCR in this developmental process remains controversial. Here we generated a non-transgenic and polyclonal model of reduced TCR expression and signal strength selectively on γδ T cells. Mice haploinsufficient for both CD3γ and CD3δ (CD3DH) showed normal αβ thymocyte subsets but specific defects in γδ T cell development, namely impaired differentiation of IL-17-producing embryonic Vγ6+ (but not adult Vγ4+) γδ T cells and a marked depletion of IFN-γ-producing CD122+ NK1.1+ (Vγ1-biased) γδ T cells throughout life. As result, adult CD3DH mice showed defective peripheral IFN-γ responses and were resistant to experimental cerebral malaria. Thus, strong TCR signaling is required within specific developmental windows with distinct Vγ usage and differential cytokine production by effector γδ T cell subsets.
2016-03-29 | GSE71637 | GEO
Project description:CD4 T cell help is critical for both the generation and maintenance of germinal centers, and T follicular helper (TFH) cells are the CD4 T cell subset required for this process. SAP (SH2D1A) expression in CD4 T cells is essential for germinal center development. However, SAP-deficient mice have only a moderate defect in TFH differentiation as defined by common TFH surface markers. CXCR5+ TFH cells are found within the germinal center as well as along the boundary regions of T/B cell zones. Here we show that germinal center associated T cells (GC TFH) can be identified by their co-expression of CXCR5 and the GL7 epitope, allowing for phenotypic and functional analysis of TFH and GC TFH populations. Here we show GC TFH are a functionally discrete subset of further polarized TFH cells, with enhanced B cell help capacity and a specialized ability to produce IL-4 in a TH2-independent manner. Strikingly, SAP-deficient mice have an absence of the GC TFH subset and SAP- TFH are defective in IL-4 and IL-21 production. We further demonstrate that SLAM (Slamf1, CD150), a surface receptor that utilizes SAP signaling, is specifically required for IL-4 production by GC TFH. GC TFH cells require IL-4 and IL-21 production for optimal help to B cells. These data illustrate complexities of SAP-dependent SLAM family receptor signaling, revealing a prominent role for SLAM receptor ligation in IL-4 production by germinal center CD4 T cells but not in TFH and GC TFH differentiation. This SuperSeries is composed of the following subset Series: GSE21379: Expression Data from WT and Sh2d1a-/- in vivo follicular helper CD4 T cells (TFH) versus non follicular helper CD4 T cells (non-TFH) GSE21380: Expression Data from in vivo Tfh vs GC Tfh vs non-Tfh Refer to individual Series
2010-04-28 | E-GEOD-21381 | biostudies-arrayexpress
Project description:Here, we discovered that the frequency of CD39+γδ Tregs, which positively correlated with poor prognosis, was significantly higher in right-sided colorectal cancer (RSCRC) than in the left-sided CRC (LSCRC). To explore the molecular mechanism leading to the difference of CD39+γδ Tregs derived from RSCRC and LSCRC, we collected fresh tissue samples of RSCRC with high expression of CD39+γδ Tregs and the LSCRC with low expression of CD39+γδ Tregs detected by flow cytometry and identified differential proteins by LC-MS based quantitative proteomic analysis with tandem mass tag (TMT)
2022-02-17 | PXD027323 | Pride