Murine gamma delta intraepithelial lymphocyte response to type I IFN and TCR blockade
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ABSTRACT:
PROVIDER: PRJNA1090425 | ENA |
REPOSITORIES: ENA
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Project description:Interferon alpha (IFNa) is a pro-inflammatory cytokine that is rapidly upregulated as part of an innate immune response. Gamma delta intraepithelial lymphocytes (gd IEL) mount a rapid antimicrobial response to luminal microorganisms and previous report indicate that the T cell receptor (TCR) of these cells is constantly triggered at steady-state. We assessed the contribution of tonic TCR activation in response to acute, systemic IFNa administration among murine gd IELs. Our data demonstrate that inhibiting basal TCR signaling has a minimal effect on the transcriptional profile of gd IELs and acute IFNa exposure induces antiviral gene programs independent of TCR signaling.
2024-10-01 | GSE262121 | GEO
Project description:Mouse small intestine intraepithelial lymphocytes (IEL) that express a ab TCR and CD8aa homodimers are an enigmatic T cell subset, as their specificity and in vivo function remain to be defined. To gain insight into the nature of these cells, we performed global gene expression profiling using microarray analysis, combined with PCR and flow cytometry to determine the level of expression of selected genes. Using these methods, TCR ab+ CD8aa IEL were compared to their TCR ab+ CD8b+ and TCR gd+ counterparts. Experiment Overall Design: In this study, the three IEL populations were isolated by cell sorting from a pool of IELs from 20 mice. RNA from each IEL subset was used to probe one microarray. A replicate experiment was performed on a seperate occasion using a new pool of 20 mice and three additional microarrays were used.
2008-06-13 | E-GEOD-5355 | biostudies-arrayexpress
Project description:Mesenteric lymph node (mLN) T cells undergo tissue adaptation upon migrating to intestinal lamina propria (LP) and intraepithelial (IE) compartments, ensuring appropriate balance between tolerance and resistance. By combining mouse genetics with single-cell and chromatin analyses, we addressed the molecular imprinting of gut epithelium on T cells. Transcriptionally, conventional and regulatory (Treg) CD4+ T cells from mLN, LP and IE segregate based on the gut layer they occupy; trajectory analysis suggests a stepwise loss of CD4-programming and acquisition of an intraepithelial profile. Treg fate–mapping coupled with RNA– and ATAC–sequencing revealed that the Treg program shuts down before an intraepithelial program becomes fully accessible at the epithelium. Ablation of CD4 lineage–defining transcription factor ThPOK results in premature acquisition of an IEL profile by mLN Tregs, partially recapitulating epithelium imprinting. Thus, coordinated replacement of circulating lymphocyte program with site–specific transcriptional and chromatin changes is necessary for tissue imprinting.
2021-01-04 | GSE146292 | GEO
Project description:Stepwise chromatin and transcriptional acquisition of an intraepithelial lymphocyte program
| PRJNA610060 | ENA
Project description:The intestinal epithelium comprises the body’s largest surface exposed to viruses. Additionally, the gut epithelium hosts a large population of intraepithelial T lymphocytes, or IELs, although their role in resistance against viral infections remain elusive. By fate-mapping T cells recruited to the murine intestine, we observed accumulation of newly recruited CD4+ T cells after infection with murine norovirus CR6 and adenovirus type-2 (AdV), but not reovirus. CR6 and AdV-recruited intraepithelial CD4+ T cells co-express Ly6A and CCR9, exhibit T helper 1 and cytotoxic profiles and confer protection against AdV in vivo and in an organoid model in an IFN-g-dependent manner. Ablation of the T cell receptor (TCR) or the transcription factor ThPOK in CD4+ T cells prior to AdV infection prevented viral control, while TCR ablation during infection did not impact viral clearance. These results uncover a protective role for intraepithelial Ly6A+CCR9+CD4+ T cells against enteric adenovirus.
2022-05-26 | GSE196417 | GEO
Project description:Conventional CD4 and CD8 single positive T cell lineages constitute the main differentiation pathway in the thymus. In human thymus, a minor TCRαβ differentiation pathway diverges from the early double positive stage, consisting of CD10+ PD-1+ cells. These cells are phenotypically and functionally similar to murine agonist-selected intraepithelial T lymphocyte precursors (IELps) which home to the small intestine. Here, the progeny of the human agonist-selected IEL lineage was identified in antigen-inexperienced cord blood (CB) with a polyclonal T cell receptor (TCR) repertoire exhibiting a bias towards early TCR alpha chain rearrangements and elevated autoreactive indices. Single-cell RNA sequencing allowed further delineation of this unconventional lineage in CB. Trajectory analysis, along with TCR repertoire analysis and transcriptomics, suggests a precursor-progeny relationship with the thymic IELps. The distinct, heterogeneous CB population can now be defined as CD3+ TCRαβ+ CD4- CCR7- CD26-. Besides recent thymic emigrants, this population also consists of newly identified effector clusters and previously described populations: the suppressive NK receptor expressing CD8+ Treg population, the KIR/NKG2A+ EOMES+ virtual memory population and the CD8αα+ T cell populations. The population shows a discriminating stable Helios expression and is exclusively able to downregulate CD8β expression, resulting in double negative T cells. The functional properties of this population suggest that the cells expand on inflammatory cues and exert cytotoxic and proinflammatory activity.
2023-03-07 | GSE201810 | GEO
Project description:Exploring TCR-like CAR-Engineered Lymphocyte Cytotoxicity against MAGE-A4
| PRJNA998572 | ENA
Project description:Conventional CD4 and CD8 single positive T cell lineages constitute the main differentiation pathway in the thymus. In human thymus, a minor TCRαβ differentiation pathway diverges from the early double positive stage, consisting of CD10+ PD-1+ cells. These cells are phenotypically and functionally similar to murine agonist-selected intraepithelial T lymphocyte precursors (IELps) which home to the small intestine. Here, the progeny of the human agonist-selected IEL lineage was identified in antigen-inexperienced cord blood (CB) with a polyclonal T cell receptor (TCR) repertoire exhibiting a bias towards early TCR alpha chain rearrangements and elevated autoreactive indices. Single-cell RNA sequencing allowed further delineation of this unconventional lineage in CB. Trajectory analysis, along with TCR repertoire analysis, transcriptomics and proteomics, suggests a precursor-progeny relationship with the thymic IELps. The distinct, heterogeneous CB population can now be defined as CD3+ TCRαβ+ CD4- CCR7- CD26-. Besides recent thymic emigrants, this population also consists of newly identified effector clusters and previously described populations: the suppressive NK receptor expressing CD8+ Treg population, the KIR/NKG2A+ EOMES+ virtual memory population and the CD8αα+ T cell populations. The population shows a discriminating stable HELIOS expression and is exclusively able to downregulate CD8β expression, resulting in double negative T cells. The functional properties of this population suggest that the cells expand on inflammatory cues and exert cytotoxic and proinflammatory activity.
2023-02-10 | PXD033392 | Pride
Project description:BCL6 is required for the thymic development of TCRαβ+CD8αα+ intraepithelial lymphocyte lineage
| PRJNA1041854 | ENA
Project description:gamma delta intraepithelial lymphocytes were isolated from the colons of DSS-treated and untreated mice. Total RNAs were isolated and compared by Affymetrix DNA microarray. Duplicate comparisons were made between DSS-treated and untreated gamma delta intraepithelial lymphocytes.
2008-12-18 | E-GEOD-13946 | biostudies-arrayexpress