TLR9 deficiency promotes CD73 expression in T cells and diabetes protection in NOD mice
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE48781 | GEO | 2013/07/11
SECONDARY ACCESSION(S): PRJNA211749
REPOSITORIES: GEO
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Project description:Analyze the effect of TLR9 deficiency on immue cell function at the gene expression level. Our hypothesis was that TLR9 deficiency promotes CD73 expression in T cells thus regulates autoimmune diabetes development in NOD mice. Sorted TCRb+ cells were pooled from several mice for furhter RNA extraction and cRNA labeling.
2013-07-11 | E-GEOD-48781 | biostudies-arrayexpress
Project description:TLR9-deficient (TLR9?/?) NOD mice develop a significantly reduced incidence of diabetes. This study was to investigate the molecular mechanisms of the protective role of TLR9 deficiency. Through gene screening and confirmation by both mRNA and protein expression, we found a significant increase in CD73-expressing immune cells from peripheral lymphoid tissues in TLR9?/? NOD mice. The elevated frequency of CD73-expressing immune cells seemed to be specific for TLR9 deficiency and was MyD88 independent. Moreover, the increased frequency of CD73 expression was limited to the NOD background. Increased frequency of CD73 expression was also associated with lower levels of proinflammatory cytokines and more anti-inflammatory cytokine production in CD4? T cells in TLR9?/? NOD mice. Purified CD73?CD4? T cells showed stronger immunosuppressive function in vitro and delayed diabetes development in vivo. The immunosuppression appeared to be mediated by TGF-?. In addition, elevated frequency of CD73-expressing cells was associated with improved ? cell function. Our observations were further confirmed by protection from diabetes with similar alterations in CD73 in the NY8.3 TCR NOD mouse model crossed with TLR9?/? mice and by the use of a TLR9 inhibitor in NOD mice. Our novel findings suggest an important immune-regulatory role of CD73 in regulation of diabetes development and may offer a new therapeutic strategy for specific intervention to prevent type 1 diabetes.
| S-EPMC3788667 | biostudies-literature
Project description:We generate B-cell-specific Tlr9-deficient (Tlr9fl/fl/Cd19Cre+/-, KO) B6 mice and model obesity using a high-fat diet. Compared with control mice, B cell Tlr9-deficient mice exhibited increased weight gain, impaired glucose and insulin tolerance, reduced IL-10-producing B cells and increased inflammation in fat tissues. Tlr9 deficiency affected B cell differentiation, immunoglobulin levels, and T cell subsets. Furthermore, altered gut microbiota in B-cell-specific Tlr9-deficient mice led to a pro-inflammatory status in gut associated lymphoid tissues and glucose metabolism dysregulation. Using 16S rRNA sequencing we report altered gut microbial communities in the KO mice. Indeed, a reduction in Lachnospiraceae, may play a key role in the observed metabolic phenotypes in KO mice. Also, We identify an important network involving Tlr9, Irf4 and Il-10.
2024-04-11 | GSE263396 | GEO
Project description:TLR9 deficiency promotes CD73 expression in T cells and diabetes protection in NOD mice
| PRJNA211749 | ENA
Project description:MSCs are a heterogeneous population and the specific population of MSCs may exhibit a selective ability for tissue repair. The aim of our research was to adapt the CD73+ subgroup of adipose derived MSCs (AD-MSCs) for the therapy of myocardial infarction (MI). Our results revealed that CD73+ AD-MSCs played more effective role in the acceleration function of cardiac recovery by promoting angiogenesis in a rat model of MI compared to mixed AD-MSCs and CD73- AD-MSCs. Microarray analysis shows differences between CD73+ and CD73- AD-MSCs when transcription profile of these two subgroups were compared, especially in VEGF pathway.
2021-06-02 | GSE167219 | GEO
Project description:Purpose: The goal of this study was to assess if TLR9 deficiency (TLR9-/-) or TLR9 incapacity to signal through MyD88 would differentially influence the epigenetic states of ABC, in a B cell intrinsic manner. Methods : Mixed bone marrow chimeras of one-third each TLR9+/+ CD45.1/2, TLR9-/- CD45.1/1 and TLR9P915H/P915H CD45.2/2 were generated on the MRL/lpr background. From each recipient, ABC were sorted with respect to the CD45 congenic markers at [20 weeks] post chimerism. DNA was isolated using a protocol adapted from Corces et al. Samples were sequenced to obtain 20M 2x75 bp paired-end reads using an Illumina NextSeq 550 sequencer (Illumina, Inc, California, USA). Results: The majority of differences in open chromatin regions were observed between TLR9-/- and TLR9P915H ABCs. This must reflect the MyD88-independent regulatory function of TLR9 (lost in TLR9-/- and present in TLR9P915H).
2022-08-03 | GSE202103 | GEO
Project description:Vertebrates typically harbor a rich gastrointestinal microbiota, which has co-evolved with the host over millennia and is essential for several of its physiological functions, in particular maturation of the immune system. Recent studies have highlighted the importance of a single bacterial species, segmented filamentous bacteria (SFB), in inducing a robust T helper (Th)17 population in the small intestinal lamina propria (SI-LP) of the mouse gut. Consequently, SFB can promote IL-17-dependent immune and autoimmune responses, gut-associated as well as systemic, including inflammatory arthritis and experimental autoimmune encephalomyelitis. Here, we exploit the incomplete penetrance of SFB colonization of NOD mice in our animal facility to explore its impact on the incidence and course of type-1 diabetes in this prototypical, spontaneous model. There was a strong co-segregation of SFB-positivity and diabetes protection in females, but not in males, which remained relatively disease-free regardless of the SFB status. In contrast, insulitis did not depend on SFB colonization. SFB-positive, but not SFB-negative, females had a substantial population of Th17 cells in the SI-LP, which was the only significant, repeatable difference in the examined T cell compartments of the gut, pancreas or systemic lymphoid tissues. Th17 signature transcripts dominated the very limited SFB-induced molecular changes detected in SI-LP CD4+ T cells. Thus, a single bacterium, and the gut immune system alterations associated with it, can either promote or protect from autoimmunity in predisposed mouse models, likely reflecting their variable dependence on different Th subsets. All gene expression profiles were obtained from highly purified T cell populations sorted by flow cytometry. Cells were sorted from individual mice with at least four replicates generated for all groups. RNA from 1-5 x 104 cells was amplified, labeled, and hybridized to Affymetrix Mo GENE 1.0ST microarrays. Raw data were preprocessed with the RMA algorithm in GenePattern, and averaged expression values were used for analysis.
2011-06-09 | E-GEOD-29806 | biostudies-arrayexpress
Project description:Recent studies have shown that non-enzymatic function of CD73 play a key role in tumor progression, but this function of CD73 in pancreatic cancer cells has not been studied. In the present study, PANC-1 cell lines were transfected with CD73 siRNA, and proliferation ability and cell cycle was significantly inhibited. However, little is known about the mechanisms involved in CD73 regulation in tumors.
2018-07-13 | GSE117012 | GEO
Project description:Vertebrates typically harbor a rich gastrointestinal microbiota, which has co-evolved with the host over millennia and is essential for several of its physiological functions, in particular maturation of the immune system. Recent studies have highlighted the importance of a single bacterial species, segmented filamentous bacteria (SFB), in inducing a robust T helper (Th)17 population in the small intestinal lamina propria (SI-LP) of the mouse gut. Consequently, SFB can promote IL-17-dependent immune and autoimmune responses, gut-associated as well as systemic, including inflammatory arthritis and experimental autoimmune encephalomyelitis. Here, we exploit the incomplete penetrance of SFB colonization of NOD mice in our animal facility to explore its impact on the incidence and course of type-1 diabetes in this prototypical, spontaneous model. There was a strong co-segregation of SFB-positivity and diabetes protection in females, but not in males, which remained relatively disease-free regardless of the SFB status. In contrast, insulitis did not depend on SFB colonization. SFB-positive, but not SFB-negative, females had a substantial population of Th17 cells in the SI-LP, which was the only significant, repeatable difference in the examined T cell compartments of the gut, pancreas or systemic lymphoid tissues. Th17 signature transcripts dominated the very limited SFB-induced molecular changes detected in SI-LP CD4+ T cells. Thus, a single bacterium, and the gut immune system alterations associated with it, can either promote or protect from autoimmunity in predisposed mouse models, likely reflecting their variable dependence on different Th subsets.
2011-06-09 | GSE29806 | GEO
Project description:CD73 marks cells with increased mesenchymal morphologies and phenotypes. To understand the transcriptional differences in CD73+ and - cells, we performed bulk RNA-seq on the CD73 sorted cells. In this study, we investigated if and how transcriptional heterogeneity of EwS cells contributes to heterogeneity of tumor phenotypes in vivo. Digital spatial profiling and human whole transcriptome analysis interrogated transcriptomic heterogeneity in EwS CHLA10 cell line xenografts.
2023-07-10 | GSE226562 | GEO