Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

The role of Foxp3 and Tbet co-expressing Treg cells in lung carcinoma.

ABSTRACT: Despite the opposite roles of Tbet and Foxp3 in the immune system as well as in tumour biology, recent studies have demonstrated the presence of of CD4+ T cells, expressing both, Tbet and Foxp3. Although Tbet+Foxp3+ T cells are currently a subject of intense research, less is known about their biological function especially in cancer. Here we found a considerable accumulation of Tbet+Foxp3+CD4+ T cells, mediated by the immunosuppressive cytokine TGFβ in the lungs of tumour bearing mice. This is in line with previous studies, demonstrating the important role of TGFβ for the immunopathogenesis of cancer. By gathering results both in murine model and in human disease, we demonstrate that, the conversion of IFNγ producing anti-tumoral T-bet+Th1 CD4+ T cells into immunosuppressive Tbet and Foxp3-PD1 co-expressing regulatory cells could represent an additional important mechanism of TGFβ-mediated blockade of anti-tumour immunity.

SUBMITTER: Kachler K

PROVIDER: S-EPMC6136856 | biostudies-other | 2018

REPOSITORIES: biostudies-other

ACCESS DATA

Json Xml

Publications

The role of Foxp3 and Tbet co-expressing Treg cells in lung carcinoma.

Kachler Katerina K Holzinger Corinna C Trufa Denis I DI Sirbu Horia H Finotto Susetta S

Oncoimmunology 20180425 8

Despite the opposite roles of Tbet and Foxp3 in the immune system as well as in tumour biology, recent studies have demonstrated the presence of of CD4+ T cells, expressing both, Tbet and Foxp3. Although Tbet+Foxp3+ T cells are currently a subject of intense research, less is known about their biological function especially in cancer. Here we found a considerable accumulation of Tbet+Foxp3+CD4+ T cells, mediated by the immunosuppr ...[more]

PMID: 30221050

Similar Datasets

CD1d-independent NK1.1+ Treg cells are IL2-inducible Foxp3+ T cells co-expressing immunosuppressive and cytotoxic molecules.

Project description:Regulatory T cells (Treg) play pivotal roles in maintaining self-tolerance and preventing immunological diseases such as allergy and autoimmunity through their immunosuppressive properties. Although Treg cells are heterogeneous populations with distinct suppressive functions, expression of natural killer (NK) cell receptors (NKR) by these cells remains incompletely explored. Here we identified that a small population of Foxp3+CD4+ Treg cells in mice expresses the NK1.1 NKR. Furthermore, we found that rare NK1.1+ subpopulations among CD4+ Treg cells develop normally in the spleen but not the thymus through CD1d-independent pathways. Compared with NK1.1- conventional Treg cells, these NK1.1+ Treg cells express elevated Treg cell phenotypic hallmarks, pro-inflammatory cytokines, and NK cell-related cytolytic mediators. Our results suggest that NK1.1+ Treg cells are phenotypically hybrid cells sharing functional properties of both NK and Treg cells. Interestingly, NK1.1+ Treg cells preferentially expanded in response to recombinant IL2 stimulation in vitro, consistent with their increased IL2Rαβ expression. Moreover, DO11.10 T cell receptor transgenic NK1.1+ Treg cells were expanded in an ovalbumin antigen-specific manner. In the context of lipopolysaccharide-induced systemic inflammation, NK1.1+ Treg cells downregulated immunosuppressive molecules but upregulated TNFα production, indicating their plastic adaptation towards a more pro-inflammatory rather than regulatory phenotype. Collectively, we propose that NK1.1+ Treg cells might play a unique role in controlling inflammatory immune responses such as infection and autoimmunity.

| S-EPMC9513232 | biostudies-literature

Cell surface galectin-9 expressing Th cells regulate Th17 and Foxp3+ Treg development by galectin-9 secretion.

Project description:Galectin-9 (Gal-9), a ?-galactoside binding mammalian lectin, regulates immune responses by reducing pro-inflammatory IL-17-producing Th cells (Th17) and increasing anti-inflammatory Foxp3(+) regulatory T cells (Treg) in vitro and in vivo. These functions of Gal-9 are thought to be exerted by binding to receptor molecules on the cell surface. However, Gal-9 lacks a signal peptide for secretion and is predominantly located in the cytoplasm, which raises questions regarding how and which cells secrete Gal-9 in vivo. Since Gal-9 expression does not necessarily correlate with its secretion, Gal-9-secreting cells in vivo have been elusive. We report here that CD4 T cells expressing Gal-9 on the cell surface (Gal-9(+) Th cells) secrete Gal-9 upon T cell receptor (TCR) stimulation, but other CD4 T cells do not, although they express an equivalent amount of intracellular Gal-9. Gal-9(+) Th cells expressed interleukin (IL)-10 and transforming growth factor (TGF)-? but did not express Foxp3. In a co-culture experiment, Gal-9(+) Th cells regulated Th17/Treg development in a manner similar to that by exogenous Gal-9, during which the regulation by Gal-9(+) Th cells was shown to be sensitive to a Gal-9 antagonist but insensitive to IL-10 and TGF-? blockades. Further elucidation of Gal-9(+) Th cells in humans indicates a conserved role of these cells through evolution and implies the possible utility of these cells for diagnosis or treatment of immunological diseases.

| S-EPMC3492452 | biostudies-literature

Expression data from Treg cells expressing mutant FoxP3

Project description:FoxP3 is a central regulator of immunological tolerance, controlling the development and function of regulatory T (Treg) cells. To dissect the complex processes orchestrated by FoxP3, we investigated impacts of three autoimmune disease-associated missense FoxP3 mutations (i.e., I363V, A384T, R397W) through knock-in mutagenesis in mice. We investigated the impacts of these mutations on Treg cell transcriptome by microarray analysis.

2017-08-01 | GSE89654 | GEO

Human lung tumor FOXP3+ Tregs upregulate four "Treg-locking" transcription factors.

Project description:Experimental data indicate that FOXP3+ Tregs can markedly curtail host antitumor immune responses, but the properties of human intratumoral Tregs are still largely unknown, in part due to significant methodologic problems. We studied the phenotypic, functional, epigenetic, and transcriptional features of Tregs in 92 patients with non-small-cell lung cancer, comparing the features of Tregs within tumors versus corresponding blood, lung, and lymph node samples. Intratumoral Treg numbers and suppressive function were significantly increased compared with all other sites but did not display a distinctive phenotype by flow cytometry. However, by undertaking simultaneous evaluation of mRNA and protein expression at the single-cell level, we demonstrated that tumor Tregs have a phenotype characterized by upregulated expression of FOXP3 mRNA and protein as well as significantly increased expression of EOS, IRF4, SATB1, and GATA1 transcription factor mRNAs. Expression of these "Treg-locking" transcription factors was positively correlated with levels of FOXP3 mRNA, with highest correlations for EOS and SATB1. EOS had an additional, FOXP3 mRNA-independent, positive correlation with FOXP3 protein in tumor Tregs. Our study identifies distinctive features of intratumoral Tregs and suggests that targeting Treg-locking transcription factors, especially EOS, may be of clinical importance for antitumor Treg-based therapy.

| S-EPMC5621877 | biostudies-other

FOXP3(+) Treg Cells and Gender Bias in Autoimmune Diseases.

Project description:CD4(+)CD25(+) regulatory T (Treg) cells play a pivotal role in the maintenance of immune homeostasis, where the X-linked master transcription factor forkhead box P3 (FOXP3) determines Treg cell development and function. Genetic deficiency of foxp3 induces dysfunction of Treg cells and immuno-dysregulation, polyendocrinopathy, enteropathy, and X-linked syndrome in humans. Functionally deficient Treg cells or the development of exTreg cells positively correlate with autoimmune diseases, such as systemic lupus erythematosus (SLE), multiple sclerosis (MS), and ankylosing spondylitis (AS). In general, females are more susceptible to SLE and MS but less susceptible to AS, where the expression of FOXP3 and its protein complex are perturbed by multiple factors, including hormonal fluctuations, inflammatory cytokines, and danger signals. Therefore, it is critical to explore the potential molecular mechanisms involved and these differences linked to gender. Here, we review recent findings on the regulation of FOXP3 activity in Treg cells and also discuss gender difference in the determination of Treg cell function in autoimmune diseases.

| S-EPMC4585344 | biostudies-literature

Antigen-non-specific regulation centered on CD25+Foxp3+ Treg cells.

Project description:CD4(+)CD25(+)Foxp3(+) regulatory T cells (Tregs) are of special interest in immunology because of their potent inhibitory function. Many fundamental aspects of Tregs, including their antigenic profile, development and peripheral homeostasis, remain highly controversial. Here, we propose a Treg-centered antigen-non-specific immunoregulation model focused on the T-cell system, particularly on CD4(+) T cells. The T-cell pool consists of naive T cells (Tnais), Tregs and effector T cells (Teffs). Regardless of antigen specificity, the ratio of the activated T-cell subsets (Treg/Teff/Tnai) and their temporal and spatial uniformity dictate the differentiation of Tnais. Activated Tregs inhibit the activation, proliferation, induction and activity of Teffs; in contrast, activated Teffs inhibit the induction of Tregs from Tnais but cooperate with Treg-specific antigens to promote the proliferation and activity of Tregs. In many cases, these interactions are antigen-non-specific, whereas the activation of both Tregs and Teffs is antigen-specific. Memory T-cell subsets are essential for the maintenance of adaptive immune responses, but the antigen-non-specific interactions among T-cell subsets may be more important during the establishment of the adaptive immune system to a newly encountered antigen. This is especially important when new and memory antigens are presented closely-both temporally and spatially-to T cells, because there are always baseline levels of activated Tregs, which are usually higher than levels of memory T cells for new antigens. Based on this hypothesis, we further infer that, under physiological conditions, Tregs in lymph nodes mainly recognize antigens frequently released from draining tissues, and that these self-reactive Tregs are commonly involved in the establishment of adaptive immunity to new antigens and in the feedback control of excessive responses to pathogens.

| S-EPMC3094156 | biostudies-other

Genetic tracing reveals transcription factor Foxp3-dependent and Foxp3-independent functionality of peripherally induced Treg cells.

Project description:Regulatory T (Treg) cells expressing the transcription factor Foxp3 are an essential suppressive T cell lineage of dual origin: Foxp3 induction in thymocytes and mature CD4+ T cells gives rise to thymic (tTreg) and peripheral (pTreg) Treg cells, respectively. While tTreg cells suppress autoimmunity, pTreg cells enforce tolerance to food and commensal microbiota. However, the role of Foxp3 in pTreg cells and the mechanisms supporting their differentiation remain poorly understood. Here, we used genetic tracing to identify microbiota-induced pTreg cells and found that many of their distinguishing features were Foxp3 independent. Lineage-committed, microbiota-dependent pTreg-like cells persisted in the colon in the absence of Foxp3. While Foxp3 was critical for the suppression of a Th17 cell program, colitis, and mastocytosis, pTreg cells suppressed colonic effector T cell expansion in a Foxp3-independent manner. Thus, Foxp3 and the tolerogenic signals that precede and promote its expression independently confer distinct facets of pTreg functionality.

| S-EPMC9885886 | biostudies-literature

Cancer-FOXP3 directly activated CCL5 to recruit FOXP3+Treg cells in pancreatic ductal adenocarcinoma.

Project description:Forkheadbox protein 3 (FOXP3), initially identified as a key transcription factor for regulatory T cells (Treg cells), was also expressed in many tumors including pancreatic ductal adenocarcinoma (PDAC). However, its role in PDAC progression remains elusive. In this study, we utilized 120 PDAC tissues after radical resection to detect cancer-FOXP3 and Treg cells by immunohistochemistry and evaluated clinical and pathological features of these patients. Cancer-FOXP3 was positively correlated with Treg cells accumulation in tumor tissues derived from PDAC patients. In addition, high cancer-FOXP3 expression was associated with increased tumor volumes and poor prognosis in PDAC especially combined with high levels of Treg cells. Overexpression of cancer-FOXP3 promoted the tumor growth in immunocompetent syngeneic mice but not in immunocompromised or Treg cell-depleted mice. Furthermore, CCL5 was directly trans-activated by cancer-FOXP3 and promoted the recruitment of Treg cells from peripheral blood to the tumor site in vitro and in vivo. This finding has been further reinforced by the evidence that Treg cells recruitment by cancer-FOXP3 was impaired by neutralization of CCL5, thereby inhibiting the growth of PDAC. In conclusion, cancer-FOXP3 serves as a prognostic biomarker and a crucial determinant of immunosuppressive microenvironment via recruiting Treg cells by directly trans-activating CCL5. Therefore, cancer-FOXP3 could be used to select patients with better response to CCL5/CCR5 blockade immunotherapy.

| S-EPMC5454319 | biostudies-literature

Fel d 1-airway inflammation prevention and treatment by co-immunization vaccine via induction of CD4+CD25-Foxp3+ Treg cells.

Project description:Pet allergens are major causes for asthma and allergic rhinitis. Fel d 1 protein, a key pet allergen from domestic cat, can sensitize host and trigger asthma attack. In this study, we report that co-immunization with recombinant Fel d 1 protein (rFel d 1) plus plasmid DNA that contains Fe1 d 1 gene was effective in preventing and treating the natural Fel d 1 (nFel d 1) induced allergic airway inflammation in mice. A population of T regulatory cells (iTreg) exhibiting a CD4+CD25-Foxp3+ phenotype and expressing IL-10 and TGF-? was induced by this co-immunization strategy. Furthermore, after adoptive transfers of the iTreg cells, mice that were pre-sensitized and challenged with nFel d 1 exhibited less signs of allergic inflammation, AHR and a reduced allergic immune response. These data indicate that co-immunization with DNA and protein mixture vaccine may be an effective treatment for cat allergy.

| S-EPMC3899136 | biostudies-literature

Post-Translational Regulations of Foxp3 in Treg Cells and Their Therapeutic Applications.

Project description:Regulatory T (Treg) cells are indispensable for immune homeostasis due to their roles in peripheral tolerance. As the master transcription factor of Treg cells, Forkhead box P3 (Foxp3) strongly regulates Treg function and plasticity. Because of this, considerable research efforts have been directed at elucidating the mechanisms controlling Foxp3 and its co-regulators. Such work is not only advancing our understanding on Treg cell biology, but also uncovering novel targets for clinical manipulation in autoimmune diseases, organ transplantation, and tumor therapies. Recently, many studies have explored the post-translational regulation of Foxp3, which have shown that acetylation, phosphorylation, glycosylation, methylation, and ubiquitination are important for determining Foxp3 function and plasticity. Additionally, some of these targets have been implicated to have great therapeutic values. In this review, we will discuss emerging evidence of post-translational regulations on Foxp3 in Treg cells and their exciting therapeutic applications.

| S-EPMC8071870 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data