Homo sapiens
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ABSTRACT:
PROVIDER: PRJNA214787 | ENA |
REPOSITORIES: ENA
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Project description:The aim of this study was to characterize the transcriptional signature of MDR1+ human memory T cells isolated from clinically inflamed gut tissue, and compare it to local MDR1- memory T cells Human mononuclear cells were isolated from the peripheral blood of a healthy adult donor (Ficol density centrifugation) or from resected lesioned gut tissue of a patient with active Crohn's disease. For cell isolation from gut tissue, tissue was rinsed with PBS, treated with 0.15% DTT to remove mucous, then with 1 mM EDTA to remove epithelial cells and intra-epithelial lymphocytes. Remaining tissue was digested using Liberase-TL (Roche) plus 10 U/mL DNase I. Mononuclear cells were then filtered through 70 mM nylon filters and isolated via a 30%/ 70% Percol gradient. Mononuclear cells from blood or gut tissue were FACS-sorted into CD3+ CD4+ CD45RO+ MDR1+ or MDR1- memory T cells, using Rhodamine 123 (Rh123) efflux as a surrogate for MDR1 expression/ activity. Sorted cells were harvested directly ex vivo (without further in vitro culture or manipulation) prior to RNA extraction. MDR1- memory CD4+ T cells vs. MDR1+ memory CD4+ T cells from healthy donor peripheral blood or from active Crohn's disease lesioned tissue; MDR1- or MDR1+ memory CD4+ T cells from blood vs. inflamed gut tissue
2013-12-17 | E-GEOD-49702 | biostudies-arrayexpress
Project description:The aim of this study was to characterize the transcriptional signature of MDR1+ human memory T cells isolated from clinically inflamed gut tissue, and compare it to local MDR1- memory T cells
2013-12-17 | GSE49702 | GEO
Project description:CD11b+ cell populations, especially macrophages are highly heterogeneous tissue resident immune cells in both mice and human. Exact subsets and their phenotype remain unknown. We here analyzed gut CD11b+ cell populations using scRNA-seq in normal, inflamed and Nlrc4 deficient mice. There existed twelve CD11b+ cell populations and subsets in SPF mice. These CD11b+ subsets were changeable dependent on inflammation and gut environment. We found consistent high expression of Ly6C, Cd62L, previously undescribed Trem1 and Ccr7 in Ly6Chigh macrophages and Cd206 and Cx3cr1 in Ly6Clow/neg cell population in different mice. However, signature genes showed that resident macrophages but not inflammatory macrophages were highly conserved in normal and inflamed mice. Gut microbiota play a role in accumulation and differentiation of gut macrophages. Both Ly6Chigh and Ly6Clow macrophages in intestine and colon tissues are similar. These uncover the transcriptional landscape and phenotypic heterogeneity of CD11b+ cells, especially macrophages in gut tissues.
2019-10-16 | GSE138902 | GEO
Project description:Inflammatory bowel diseases are associated with dysregulated immune responses in the intestinal tissue. Four molecularly identified macrophage subsets control immune homeostasis in healthy gut. However, the specific roles and transcriptomic profiles of the phenotypically heterogeneous CD14+ macrophage-like population in inflamed gut remain to be investigated in Crohn’s disease (CD). Here we identified two phenotypically, morphologically and functionally distinct colonic HLADR+SIRPα+CD14+ subpopulations that were further characterized using single-cell RNA-sequencing (scRNAseq) in CD. Frequencies of CD64hiCD163−/dim cells selectively augmented in inflamed colon and correlated with endoscopic score of disease severity. IL-1β and IL-23-producing CD64hiCD163−/dim cells predominated over TNF-α-producing CD64hiCD163hi cells in lesions. Purified “inflammatory monocyte-like” CD163−, but not “macrophage-like” CD163hi cells, through IL-1β, promoted Th17/Th1 but not Th1 responses in tissue memory CD4+T cells. Unsupervised scRNAseq analysis that captures the entire HLADR+SIRPα+ population revealed six clusters, two of which were enriched in either CD163− or CD163hi cells, and best defined by TREM1/FCAR/FCN1/IL1RN or CD209/MERTK/MRCI/CD163L1 genes, respectively. Selected newly identified discriminating markers were used beyond CD163 to isolate cells that shared pro-Th17/Th1 function with CD163− cells. In conclusion, a molecularly distinct pro-inflammatory CD14+ subpopulation accumulates in inflamed colon, drives intestinal inflammatory T-cell responses, and thus, might contribute to CD disease severity.
2019-11-09 | GSE140123 | GEO
Project description:Multidrug resistance (MDR)-1 acts as a chemotherapeutic drug efflux pump in tumor cells, although its physiologic functions remain enigmatic. Using a recently-developed MDR1-knockin reporter allele (Abcb1aAME/+), we found that constitutive MDR1 expression amongst hematopoietic cells was observed mainly in cytolytic lymphocytes—including CD8+ cytotoxic T lymphocytes (CTL) and natural killer cells—and regulated by Runt-related (Runx) transcription factors. Although MDR1 was dispensable for naïve CD8+ T cell development, it was required for both normal accumulation of effector CTL following acute viral infection and protective function of memory CTL upon challenge with an intracellular bacterium. MDR1 acted early after naïve CD8+ T cell activation to suppress oxidative stress, enforce survival and safeguard mitochondrial function in developing CTL. Together, these data highlight an important endogenous function of MDR1 in cell-mediated immune responses, and suggest that ongoing efforts to intentionally inhibit MDR1 in cancer patients could be counter-productive.
2020-02-28 | GSE143140 | GEO
Project description:Multidrug resistance (MDR)-1 acts as a chemotherapeutic drug efflux pump in tumor cells, although its physiologic functions remain enigmatic. Using a recently-developed MDR1-knockin reporter allele (Abcb1aAME/+), we found that constitutive MDR1 expression amongst hematopoietic cells was observed mainly in cytolytic lymphocytes—including CD8+ cytotoxic T lymphocytes (CTL) and natural killer cells—and regulated by Runt-related (Runx) transcription factors. Although MDR1 was dispensable for naïve CD8+ T cell development, it was required for both normal accumulation of effector CTL following acute viral infection and protective function of memory CTL upon challenge with an intracellular bacterium. MDR1 acted early after naïve CD8+ T cell activation to suppress oxidative stress, enforce survival and safeguard mitochondrial function in developing CTL. Together, these data highlight an important endogenous function of MDR1 in cell-mediated immune responses, and suggest that ongoing efforts to intentionally inhibit MDR1 in cancer patients could be counter-productive.
2020-02-28 | GSE143139 | GEO
Project description:Antigen-experienced (or memory) T lymphocytes were isolated from the synovial fluid of inflamed joints and the peripheral blood of patients with juvenile idiopathic arthritis (JIA). After flow-sort of CD4+CD45RO+CD25- (Tcon), CD4+CD45RO+CD127loCD25+ (Treg) and CD8+CD45RO+ T cells, single-cell RNA-sequencing was conducted to perform paired analyses of gene transcription and T cell receptor (TCR) repertoires in the same cells. The study aimed to identify T memory cells that were stimulated by antigens in inflamed joints of JIA patients and which perpetuate chronic inflammation by expression pro-inflammatory genes. In addition, the study aimed at understanding the clonal relationships of T cells differentiating at chronically inflamed sites, as well as to identify blood-circulating T cell clones that shared gene expression and antigen-specificity with T cells in inflamed joints in order to improve patient stratification and diagnostics of patients with chronic inflammatory diseases in the future.
2020-11-27 | GSE160097 | GEO
Project description:Multidrug resistance (MDR)-1 acts as a chemotherapeutic drug efflux pump in tumor cells, although its physiologic functions remain enigmatic. Using a recently-developed MDR1-knockin reporter allele (Abcb1aAME/+), we found that constitutive MDR1 expression amongst hematopoietic cells was observed mainly in cytolytic lymphocytes—including CD8+ cytotoxic T lymphocytes (CTL) and natural killer cells—and regulated by Runt-related (Runx) transcription factors. Although MDR1 was dispensable for naïve CD8+ T cell development, it was required for both normal accumulation of effector CTL following acute viral infection and protective function of memory CTL upon challenge with an intracellular bacterium. MDR1 acted early after naïve CD8+ T cell activation to suppress oxidative stress, enforce survival and safeguard mitochondrial function in developing CTL. Together, these data highlight an important endogenous function of MDR1 in cell-mediated immune responses, and suggest that ongoing efforts to intentionally inhibit MDR1 in cancer patients could be counter-productive. This SuperSeries is composed of the SubSeries listed below.
2020-02-27 | GSE143141 | GEO
Project description:The vast majority of currently licensed human vaccines work on the basis of long-term protective antibody responses. Generation of long term humoral immunity is a complex process predominantly dependent on germinal centers and CD4 T cell help to B cells. Follicular helper T cells (Tfh) are the specialized CD4 T cells for B cell help. However, whether such cells develop memory in humans and can be tracked in human blood has been enigmatic. We identified a subpopulation of blood CXCR5+ PD-1+CXCR3- resting CD4 T cells that are most related to Tfh cells of lymphoid tissue by gene expression profile and phenotype. Functional analysis showed that these memory Tfh cells were specialized for helping B cells. Moreover, these cells correlate with a clinically important outcome: development of potent neutralizing antibodies against HIV in HIV+ individuals. CD4 T cells were enriched from fresh blood of 5 normal donors by magnetic beads negative selection. Following enrichment, CD14-CD16-CD19-CD8-CD4+CD45RA- cells from each donor were FACS sorted into the following 5 populations: CXCR5-, CXCR5+PD1+CXCR3-, CXCR5+PD1+CXCR3+, CXCR5+PD1-CXCR3-, and CXCR5+PD1-CXCR3+. The gene expression profile of each cell population was determined.
2013-11-12 | E-GEOD-50390 | biostudies-arrayexpress
Project description:Monocyte maturation program into macrophages (MΦ) is well-defined in murine gut under homeostatic or inflammatory conditions. Obviously, in vivo tracking of monocytes in inflamed tissues remains difficult in humans. Furthermore, in vitro models fall short in generating the surrogates of transient extravasated tissue inflammatory monocytes. Here, we aimed to unravel environmental cues that replicate in vitro the human monocyte “waterfall” process by first generating tissue-like inflammatory monocytes, and then shifted them towards MΦ. Purified CD14+CD16- monocytes cultured with granulocyte-macrophage colony-stimulating factor (GM-CSF), IFNg and IL23 differentiated into CD14+CD163- cells displayed a monocyte-like morphology. The in vitro generated inflammatory CD14+CD163- cells (Infl mo-like), like the CD14+CD163- mo-like cells that accumulate in inflamed colon of Crohn’s disease patients, promoted IL-1β-dependent memory Th17 and Th17/Th1 responses. Next, in vitro generated Infl mo-like cells converted to functional CD163+ MΦ following exposure to TGFβ and IL10. Gene set enrichment analysis further revealed a shared molecular signature between converted CD163+ MΦ and MΦ detected in various inflamed non-lymphoid and lymphoid diseased tissues. Our findings propose a two-step in vitro culture that recapitulates human monocyte maturation cascade in inflamed tissue. Manipulating this process might open therapeutic avenues for chronic inflammatory disorders. Classical CD14+CD16- human monocytes were sorted and cultured for 6 days with GM-CSF+IFNg+IL23, leading to the generation of CD163- d6 cells. Following the 6 days culture with GM-CSF+IFNg+IL23, TGFβ+IL10 were added for another 6 days. This gave rise to the CD163+ d12 and CD163- d12 populations. We used microarray (Clariom D, Affymetrix) to observe molecular differences in the 3 in vitro generated populations: (1) CD163- d6 (2) CD163+ d12 (3) CD163- d12.
2020-06-23 | GSE149722 | GEO