Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Human GPR15 deficiency reveals CD8+ T regulatory cell-macrophage crosstalk in intestinal inflammation

ABSTRACT: We employed a CITE-seq combined with single-cell sequencing approach using 10x Genomics scRNA-seq to analyze peripheral and intestinal lymphocytes from Gpr15⁻/⁻ mice and from patients carrying deleterious GPR15 mutations. We show that GPR15, a G protein–coupled receptor (GPCR) expressed in immune cells and previously described as an entry co-factor for human and simian immunodeficiency viruses, serves as a crucial marker and homing receptor for a unique subset of intramucosal GPR15-guided regulatory CD8⁺ T lymphocytes (CD8⁺ TIGR cells). Our results demonstrate that deleterious GPR15 variants in humans impair the homing of CD8⁺ TIGR cells, leading to severe early-onset inflammatory bowel disease (IBD). In mice, GPR15 deficiency disrupts the colonic recruitment of CD8⁺ TIGR cells, causing an accumulation of inflammatory macrophages and heightened susceptibility to colitis. Together, our findings identify CD8⁺ TIGR cells as a previously unrecognized component of organ-specific immune regulation and reveal potential therapeutic avenues for the treatment of IBD.

ORGANISM(S): Mus musculus Homo sapiens

PROVIDER: GSE314446 | GEO | 2026/05/05

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Ahr-Foxp3-RORγt Axis Controls Gut Homing of CD4+ T Cells by Regulating GPR15

Project description:The orphan chemoattractant receptor GPR15 is important for homing T lymphocytes to the large intestine, thereby maintaining intestinal immune homeostasis. However, the molecular mechanisms underlying the regulation of GPR15 expression remain elusive. Here we show a central role of the aryl hydrocarbon receptor (Ahr) in promoting GPR15 expression both in mice and human, thus gut homing of T lymphocytes. Mechanistically, Ahr directly binds to open chromatin regions of the Gpr15 locus to enhance its expression. Ahr transcriptional activity in directing GPR15 expression was modulated by two transcription factors, Foxp3 and RORγt, both of which are expressed preferentially by gut Tregs in vivo. Specifically, Foxp3 interacted with Ahr and enhanced Ahr DNA binding at the Gpr15 locus, thereby promoting GPR15 expression. In contrast, RORγt plays an inhibitory role at least in part by competing with Ahr binding to the Gpr15 locus. Our findings thus demonstrate a key role for Ahr in regulating Treg intestinal homing under the steady state and during inflammation, and the importance of Ahr-RORγt-Foxp3 axis in regulating gut homing receptor GPR15 expression by lymphocytes.

2020-07-29 | GSE137171 | GEO

Expression data from GPR15+CD4+ and GPR15-CD4+ T cells in LILP

Project description:GPR15 is an orphan G-protein coupled receptor and its expression is abundant among T cells in the large intestine lamina propria. We used microarrays to examine charateristics of GPR15- vs GPR15+ CD4+ T cells in LILP and identified distinct classes of up-regulated genes in GPR15+ CD4+ T cells. We have generated GFP knock-in mice in GPR15 locus and used GFP as a maker for GPR15 expression. In heterozygous mice, GPR15+CD4+ T cells and GPR15-CD4-T cells were sorted and RNA was prepared from them.

2013-05-09 | E-GEOD-45773 | biostudies-arrayexpress

GPR15+ vs GPR15- tumor-associated Tregs

Project description:GPR15+ vs GPR15- tumor-associated Tregs were sorted from colorectal cancer mice (Foxp3-RFP x GPR15-GFP)

2021-03-12 | GSE168744 | GEO

GPR15-mediated T cell recruitment during acute viral myocarditis facilitated virus elimination and improved outcome

Project description:Viral myocarditis is characterised by infiltration of mononuclear cells essential for virus elimination. GPR15 has been identified as a homing receptor for regulatory T cells in inflammatory intestine diseases, but its role in inflammatory heart diseases is still elusive. Therefore, we investigated the role of GPR15 during coxsackievirus B3‑induced myocarditis utilizing GPR15‑deficient mice as well as using in vitro experiments. Here we show that GPR15 deficiency had no effect on susceptibility to virus infection, but virus elimination was scant leading to adverse cardiac remodelling and impaired cardiac function. Delayed recruitment of regulatory T cells was accompanied by prolonged persistence of cytotoxic T cells as well as regulatory T cells in GPR15-deficient mice. Further, RNA sequencing revealed prolonged inflammatory response and altered chemotaxis in GPR15-deficient mice. In line, we identified GPR15 and its ligand GPR15L as an important chemokine receptor-ligand pair for the recruitment of regulatory and cytotoxic T cells. In summary, the insufficient virus elimination might be caused by a delayed recruitment of T cells as well as delayed interferon-γ expression, resulting in a prolonged inflammatory response and an adverse outcome in GPR15-deficient mice.

2023-11-24 | GSE248521 | GEO

Expression data from GPR15+CD4+ and GPR15-CD4+ T cells in LILP

2013-05-09 | GSE45773 | GEO

GPR15+ vs GPR15- tumor-associated Tregs

Project description:GPR15+ vs GPR15- tumor-associated Tregs

| PRJNA713801 | ENA

Specific induction of GPR15 expression in heterogeneous blood lymphocytes by smoking

Project description:Although a mucosal and cutaneous chemokine ligand for G protein –linked receptor GPR15 was recently identified, the physiological role of GPR15 remains yet elusive. In blood, in has been shown that smoking is, to date, the only specific condition leading to an increase in GPR15+ T cells. We therefore used transcriptome sequencing to describe GPR15-expressing blood T cells in more detail.

2019-01-04 | GSE114837 | GEO

Gene expression profiles of GPR15 knock out macrophages

Project description:To confirm the changed gene expression profiles in GPR15 knock out (KO) macrophages, we applied a SurePrint G3 Mouse Gene Expression service from Takara Bio Inc (Kusatsu, Shiga, Japan) to analyze gene expression profiles in lipopolysaccharide (LPS)-stimulated GPR15KO macrophages, comparing with wild type (WT) macrophages. Most significantly up-regulated genes in GPR15KO macropahges included Il6, Il17a, Il23, Tnfsf8, Il1b, Ifna2 and Ccnd2. On the contrary, several inflammation-related genes, including Ccl17, Itgax, Nrp1 and Rasgrf2, were down-regulated in WT macrophages, compared to GPR15 KO macrophages. Abdominal macrophages from WT and GPR15 KO mice were stimulated with PBS or LPS (100 ng/ml) for 4 hrs. Total RNA were extracted using a TRIzol-chloroform based method.

2016-08-25 | E-GEOD-86020 | biostudies-arrayexpress

Clonally expanded, GPR15-expressing pathogenic effector Th2 cells are associated with eosinophilic esophagitis

Project description:Eosinophilic esophagitis (EoE) is an allergic disorder characterized by the recruitment of eosinophils to the esophagus, resulting in chronic inflammation. We sought to understand the cellular populations present in the esophageal biopsies of patients with EoE and to determine how these populations are altered between active disease and remission. To this end, we analyzed cells from the esophageal biopsies, duodenal biopsies, and peripheral blood of EoE patients in active disease or remission using single-cell RNA and TCR sequencing. We identified gene modules regulated by transcription factors from the NF-κB family that characterize activated eosinophils in patients with active disease. Pathogenic effector Th2 (peTh2) cells present in the esophageal biopsies of patients with active disease expressed unique gene signatures associated with the synthesis of eicosanoids that are predicted to directly promote activation of tissue-resident eosinophils. The tissue-resident peTh2 population also exhibited clonal expansion, suggesting antigen-specific activation. Peripheral CRTH2+CD161- and CRTH2+CD161+ memory CD4+ T cells were enriched for either a conventional Th2 phenotype or a peTh2 phenotype, respectively. These cells also exhibited significant clonal expansion and convergence of TCR sequences, indicating that these cells are expanded in response to a defined set of antigens. The esophagus-homing receptor GPR15 was upregulated by peripheral peTh2 clonotypes that were also detected in the esophagus. Lastly, peTh2 cells and GPR15+ cells were enriched among milk-reactive CD4+ T cells in patients with milk-triggered disease, suggesting that peTh2 cells in EoE are an expanded, food antigen-specific population with enhanced esophagus homing potential.

2021-08-13 | GSE175930 | GEO

Ahr-Foxp3-RORγt Axis Controls Gut Homing of CD4+ T Cells by Regulating GPR15

Project description:Ahr-Foxp3-RORγt Axis Controls Gut Homing of CD4+ T Cells by Regulating GPR15

| PRJNA564732 | ENA