Regulatory T cells Maintain Lung Function Upon Infectious Damage
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE71588 | GEO | 2015/08/27
SECONDARY ACCESSION(S): PRJNA291572
REPOSITORIES: GEO
Similar Datasets
Project description:RNA-Seq analysis of Treg cell subsets isolated from lungs of Il10GFPFoxp3Thy1.1 mice. Thy1.1+ Treg cells were FACS-sorted into IL-10–IL-18R–, IL-10+IL-18R– and IL10–IL-18R+ populations on day 5 following intranasal infection with 0.5 LD50 PR8-OTI influenza virus. mRNA profiles of each Thy1.1+ Treg cell population (IL-10–IL-18R–, IL-10+IL-18R– and IL10–IL-18R+) from lungs on day 5 following influenza infection from 5 infected mice, sorted into TRIzol LS reagent.
2015-08-27 | E-GEOD-71588 | biostudies-arrayexpress
Project description:The tumor microenvironment contains high frequencies of inflammatory regulatory T (Treg) cells. These Treg exhibit superior regulatory function compared with those from other environments such as the spleen, partially due to expression of anti-inflammatory interleukin-10. In order to gain insight into the origins and functional roles of different Treg subsets, we used whole genome microarray analysis to characterize tumor IL-10+ and tumor IL-10- Treg subsets obtained from VERT-X reporter mice bearing transplantable tumors, along with total tumor Treg and spleen Treg from FoxP3-EGFP reporter mice. Few genes were found to differ between IL-10+ and IL-10- tumor Treg subsets (29 upregulated, 88 downregulated), suggesting a common origin of each Treg subset. The specific gene expression profile of IL-10+ tumor Treg was associated with the tumor microenvironment and absent from spleen Treg, suggesting it to be driven by components of the inflammatory tumor microenvironment. The IL-10+ tumor Treg gene expression profile displayed upregulation of genes associated with a higher activation state and greater effector function. Pooled MC38 tumor tissue from VERT-X or FoxP3-EGFP reporter mice were used to obtain IL10+ tumor Treg (VERT-X), IL10- tumor Treg (VERT-X) and total tumor Treg (FoxP3-EGFP). Spleens from tumor-free FoxP3-EGFP mice were used for spleen Treg. Three experiments for each population gave a total 12 RNA samples.
2013-08-31 | E-GEOD-49380 | biostudies-arrayexpress
Project description:Induced Treg (iTreg) cells are essential for tolerance and can be used therapeutically, yet their stability in vivo and mechanisms of suppression are unresolved. Here, we used a treatment model of colitis to examine the role of autologous IL-10 in iTreg cell function. Mice treated with IL-10+/+ iTreg cells in combination with IL-10–/– natural Treg (nTreg) cells survived and gained weight, even though iTreg cells were numerically disadvantaged and comprised just ~20% of all Treg cells in treated mice. Notably, ~85% of the transferred iTreg cells lost Foxp3 expression (ex-iTreg) but retained a portion of the iTreg transcriptome which failed to limit their pathogenic potential. The TCR repertoires of iTreg and ex-iTreg cells exhibited almost no overlap, which indicates that the two populations are clonally unrelated and maintained by different selective pressures. These data demonstrate a potent and critical role for iTreg cell produced IL-10 that can supplant the IL-10 produced by nTreg cells and compensate for the inherent instability of the iTreg population. BALB/c Rag1-/- mice were treated with 500,00 WT nTreg cells plus 500,000 WT in-vitro-derived iTreg cells. After 125 days cells were sorted by flow cytometry from spleens and mesenteric lymph nodes from 14 treated mice. EGFP+ Thy1.1+ iTreg cells, EGFP+ Thy1.1– nTreg cells, and EGFP–Thy1.1+ ex-iTreg cells were pooled and used to generate total RNA for each iTreg, nTreg, and ex-iTreg array set, which was labeled and hybridized to Affymetrix 430 2.0 GeneChips in accordance to the manufacturer’s protocol. Two sets of arrays were performed, and the results were averaged. Both iTreg and nTreg array sets were compared to a) naïve CD4+EGFP– Tconv cells from Foxp3EGFP. The subset of probe sets whose expression increased or decreased by twofold or more relative to Tconv cells as a common standard was identified and used for further analysis.
2012-12-06 | E-GEOD-35543 | biostudies-arrayexpress
Project description:RAR-related orphan receptor gamma (ROR t)-expressing regulatory T (ROR t+ Treg) cells play pivotal roles in preventing T cell hyperactivation and maintaining tissue homeostasis, in part, by secreting the anti-inflammation cytokine interleukin 10 (IL-10). Here, we report that Hypoxia Induced Factor 1a (HIF1alpha) is the master transcription factor for *Il10* in ROR t+ Tregs. Interestingly, this critical anti-inflammatory pathway is negatively regulated by an RNA-binding protein DEAD box helicase 5 (DDX5). As a transcriptional corepressor, DDX5 restricts the expression of HIF1 and its downstream target gene *Il10* in ROR t+ Tregs. T cell specific *Ddx5* knockout (DDX5 T) mice have augmented ROR t+ Treg suppressor activities and are better protected from intestinal inflammation. Genetic ablation or pharmacologic inhibition of HIF1a restores enteropathy susceptibility in DDX5 T mice. The DDX5-HIF1 -IL-10 pathway is conserved in mice and humans. These findings reveal potential therapeutic targets for intestinal inflammatory diseases.
2022-12-21 | GSE157259 | GEO
Project description:Bone marrow-derived macrophages were produced from mice lacking IL-10 alone (IL10-def) or mice lacking both IL-10 and the p50/p105 subunit of NF-kB (p50/IL10), and left unstimulated, stimulated with LPS (1 ng/ml) or stimulated with LPS and IL-10 (0.3 ng/ml).
2011-01-10 | GSE19941 | GEO
Project description:The effects of IL-33 on ST2+ Treg cells were not studied thouroughly. We FACS-sorted in vitro expanded ST2+ Treg cells from C57BL/6 Foxp3-IRES-mRFP (B6 FIR) mice. We next used RNA-seq techonology to define how recombinant IL-33 (rIL-33) may impact mouse Treg by to assessing the transcriptome of IL-33-stimulated ST2+ Treg cells compared to that of untreated ST2+ Treg cells. Our data revealed that ST2+ Treg stimulated with rIL-33 for 6 hours exhibited increased expression of Il10 and Il13 compared to unstimulated ST2+ Treg cells.
2019-05-17 | GSE123922 | GEO
Project description:Background: The mechanisms underlying ozone (O3)-induced pulmonary inflammation remain unclear. Interleukin (IL)-10 is an anti-inflammatory cytokine that is known to inhibit inflammatory mediators. Objectives: The current study investigated the molecular mechanisms underlying IL-10-mediated attenuation of O3-induced pulmonary inflammation in mice. Methods: Il10-deficient (Il10-/-) and wild type (Il10+/+) mice were exposed to 0.3-ppm O3 or filtered air for 24, 48 or 72 hr. Immediately following exposure, differential cell counts, and total protein (a marker of lung permeability) were assessed from bronchoalveolar lavage fluid (BALF). mRNA and protein levels of cellular mediators were determined from lung homogenates. We also utilized global mRNA expression analyses of lung tissue with Ingenuity Pathway Analyses (IPA) to identify patterns of gene expression through which IL-10 modifies O3-induced inflammation. Results: Mean numbers of BALF polymorphonuclear leukocytes (PMNs) were significantly greater in Il10-/- mice than in Il10+/+ mice after exposure to O3 at all time points tested. O3-enhanced nuclear NF-kB translocation was elevated in the lungs of Il10-/- compared to Il10+/+ mice. Gene expression analyses revealed several key IL-10 and O3-dependent mediators, including IL-6, MIP-2, IL-1 and CD86. Conclusions: Results indicated that IL-10 protects against O3-induced pulmonary neutrophilic inflammation and cell proliferation. Moreover, gene expression analyses identified three response pathways and several novel genetic targets (e.g. Ccr1, Socs3, Il33, Hat1, and Gale) through which IL10 may modulate the innate and adaptive immune response. These novel mechanisms of protection against the pathogenesis of O3-induced pulmonary inflammation may also provide potential therapeutic targets to protect susceptible individuals.
2011-10-19 | GSE25095 | GEO
Project description:Human Treg IFNg/IL-10 subpopulations
| PRJNA478058 | ENA
Project description:Background: The mechanisms underlying ozone (O3)-induced pulmonary inflammation remain unclear. Interleukin (IL)-10 is an anti-inflammatory cytokine that is known to inhibit inflammatory mediators. Objectives: The current study investigated the molecular mechanisms underlying IL-10-mediated attenuation of O3-induced pulmonary inflammation in mice. Methods: Il10-deficient (Il10-/-) and wild type (Il10+/+) mice were exposed to 0.3-ppm O3 or filtered air for 24, 48 or 72 hr. Immediately following exposure, differential cell counts, and total protein (a marker of lung permeability) were assessed from bronchoalveolar lavage fluid (BALF). mRNA and protein levels of cellular mediators were determined from lung homogenates. We also utilized global mRNA expression analyses of lung tissue with Ingenuity Pathway Analyses (IPA) to identify patterns of gene expression through which IL-10 modifies O3-induced inflammation. Results: Mean numbers of BALF polymorphonuclear leukocytes (PMNs) were significantly greater in Il10-/- mice than in Il10+/+ mice after exposure to O3 at all time points tested. O3-enhanced nuclear NF-kB translocation was elevated in the lungs of Il10-/- compared to Il10+/+ mice. Gene expression analyses revealed several key IL-10 and O3-dependent mediators, including IL-6, MIP-2, IL-1 and CD86. Conclusions: Results indicated that IL-10 protects against O3-induced pulmonary neutrophilic inflammation and cell proliferation. Moreover, gene expression analyses identified three response pathways and several novel genetic targets (e.g. Ccr1, Socs3, Il33, Hat1, and Gale) through which IL10 may modulate the innate and adaptive immune response. These novel mechanisms of protection against the pathogenesis of O3-induced pulmonary inflammation may also provide potential therapeutic targets to protect susceptible individuals. PARALLEL study design with 26 samples. Biological replicates: 2 to 3 replicates per group with wild type air exposed animals as controls for each time point (24, 48, 72 hours). Time-Course, Dose-Response, Strain comparison
2011-10-18 | E-GEOD-25095 | biostudies-arrayexpress
Project description:Regulatory T (Treg) cells are essential for immune homeostasis but inhibit immune rejection of cancer. Strategies to disrupt Treg-mediated cancer immunosuppression have been met with limited clinical success, but the underlying mechanisms for this failure are poorly understood. By modeling Treg-targeted immunotherapy in mice, we find that a subset of CD4+ Foxp3- conventional T (Tconv) cells with potent suppressive function undergoes activation and expansion upon depletion of Foxp3+ Treg cells and limits therapeutic efficacy. We noted that Foxp3- Tconv cells within tumors adopt a Treg-like transcriptional profile upon Treg depletion and acquire suppressive function. This is attributable to a Th2-like subset of CD4+ Tconv cells marked by expression of (C-C motif) receptor 8 (CCR8) and enriched in Treg-associated transcripts. CCR8+ Tconv cells are found in mouse and human tumors. Upon Treg depletion, CCR8+ Tconv cells undergo systemic and intratumoral activation and expansion, resulting in IL-10 dependent suppression of anti-tumor immunity. Consequently, conditional deletion of Il10 within T cells augments anti-tumor efficacy upon Treg-depletion in mice, and antibody blockade of IL-10 signaling synergizes with Treg depletion to overcome treatment resistance. These findings reveal a secondary layer of immunosuppression by Tconv cells released upon therapeutic Treg depletion and suggest that broader consideration of suppressive function within the T cell lineage is required for development of effective Treg-targeted therapies.
2024-01-11 | GSE236824 | GEO