Expression data from sorted Treg cells from WT or motheaten mice
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE23600 | GEO | 2010/08/13
SECONDARY ACCESSION(S): PRJNA131745
REPOSITORIES: GEO
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Project description:The importance of regulatory T cells (Treg) for immune tolerance is well recognized, yet the signaling molecules influencing their suppressive activity are relatively poorly understood. We identified the cytoplasmic tyrosine phosphatase SHP-1 as a novel ‘endogenous brake’ and modifier of the suppressive ability of Treg cells; consistent with this notion, loss of SHP-1 expression strongly augments the ability of Treg cells to suppress inflammation in a mouse model. Specific harmacological inhibition of SHP-1 enzymatic activity via the cancer drug sodium stibogluconate (SSG) potently augmented Treg cell suppressor activity both in vivo and ex vivo. We evaluated the gene expression profiles of sorted T reg cells (CD4+CD25+) from wild type (wt) mice and mice that were heterozygous (he) or homozygous (me) for SHP-1 knockout (motheaten phenotype). T reg (CD4+CD25+) cells were isolated form wild type (WT) mice and that were heterozygous (he) or homozygous (me) for SHP-1 knockout (motheaten phenotype); totalRNA was isolated using Arcturus reagents; aRNA was generated and amplified using Arcturus reagents; and labeled product was hybridized to Affymetrix chips to asses gene expression patterns.
2010-08-13 | E-GEOD-23600 | biostudies-arrayexpress
Project description:A common method used both in vitro and in vivo, to identify Tregs in CD4+ T cells is through the characterization of surface marker CD25. Although CD25 expression is well correlated with regulatory activity in vitro, CD4+CD25+ T cells are not the only regulatory CD4+ T cells in vivo. Studies suggest that in many situations, CD4+CD25M-bM-^@M-^S T cells are as effective as CD4+CD25+ T cells in controlling T cell mediated disease. Therefore, CD25 is not a uniquely specific cell surface marker for the identification of Tregs. CD49f is an M-NM-16-integrin subunit which dimerizes with either the M-NM-2 1 or M-NM-2 4 subunit to form receptors for various laminin isoforms. We found that CD4+ T cells from NOD mice express CD49f, and old non-diabetic NOD mice had an increase of CD4+CD49f+ T cells in the spleen and peripheral lymph node when compared to both young and diabetic mice. This study was conducted to further characterize CD4+CD49f+ Treg cell subpopulation in NOD mice. It was found that CD4+CD49f+T cells possess suppressive ability and only one third of CD4+CD49f+ T cells expressing CD25. Based on the expression of CD49f and CD25, CD4+ T cells was divided into four populations , CD25+CD49f+ ,CD25+CD49f- ,CD25-CD49f+ but CD25-CD49f- are of suppressive ability, and we further found that Foxp3 expression was highly correlated with the suppressive ability of these three Treg populations. In conclusion our data indicate that CD49f marks a CD4+ CD25+ Treg subset with more potent suppression activity and identifies a CD25-CD4+ T cell population with suppression function in a Foxp3+ expression dependent manner. We divided CD4+ T cells into four populations: CD25+CD49f+, CD25+CD49f-, CD25-CD49f+, CD25-CD49f-; Microarray technology was used to determine gene expression differences among these four groups.
2012-05-09 | E-GEOD-30503 | biostudies-arrayexpress
Project description:A common method used both in vitro and in vivo, to identify Tregs in CD4+ T cells is through the characterization of surface marker CD25. Although CD25 expression is well correlated with regulatory activity in vitro, CD4+CD25+ T cells are not the only regulatory CD4+ T cells in vivo. Studies suggest that in many situations, CD4+CD25– T cells are as effective as CD4+CD25+ T cells in controlling T cell mediated disease. Therefore, CD25 is not a uniquely specific cell surface marker for the identification of Tregs. CD49f is an α6-integrin subunit which dimerizes with either the β 1 or β 4 subunit to form receptors for various laminin isoforms. We found that CD4+ T cells from NOD mice express CD49f, and old non-diabetic NOD mice had an increase of CD4+CD49f+ T cells in the spleen and peripheral lymph node when compared to both young and diabetic mice. This study was conducted to further characterize CD4+CD49f+ Treg cell subpopulation in NOD mice. It was found that CD4+CD49f+T cells possess suppressive ability and only one third of CD4+CD49f+ T cells expressing CD25. Based on the expression of CD49f and CD25, CD4+ T cells was divided into four populations , CD25+CD49f+ ,CD25+CD49f- ,CD25-CD49f+ but CD25-CD49f- are of suppressive ability, and we further found that Foxp3 expression was highly correlated with the suppressive ability of these three Treg populations. In conclusion our data indicate that CD49f marks a CD4+ CD25+ Treg subset with more potent suppression activity and identifies a CD25-CD4+ T cell population with suppression function in a Foxp3+ expression dependent manner.
2012-05-10 | GSE30503 | GEO
Project description:Targeting histone/protein deacetylase (HDAC)-6, -9, or Sirtuin-1 (Sirt1) augments the suppressive functions of Foxp3+ T regulatory (Treg) cells, but it is unclear if this involves different mechanisms, such that combined inhibition would be beneficial. We compared the suppressive functions of Tregs from wild-type C57BL/6 mice or mice with global (HDAC6-/-, HDAC9-/-, dual HDAC6/9-/-) or conditional deletion (CD4-Cre or Foxp3-Cre and floxed Sirt1; GSE26425) alone, or after treatment with isoform-selective HDAC inhibitors (HDACi). We found the heat shock response was crucial in mediating the effects of HDAC6, but not Sirt1 inhibition. Furthermore, while HDAC6, HDAC9 and Sirt1 all deacetylate Foxp3, each has diverse effects on Foxp3 transcription, and loss of HDAC9 is associated with stabilization of Stat5 acetylation and its transcriptional activity. Targeting different HDAC can increase Treg function by multiple and additive mechanisms, indicating the therapeutic potential for combinations of HDACi in the management of autoimmunity and alloresponses post-transplant. RNA from three independent samples of magnetically separated CD4+CD25+ Treg of HDAC9-/- mice, compared to wild type (C57BL/6) control.
2012-06-20 | E-GEOD-36095 | biostudies-arrayexpress
Project description:Regulatory T cells (Tregs) expressing the transcription factor Foxp3 constitute a unique T cell lineage committed to suppressive functions and are crucial for suppressing aberrant immune responses in autoimmunity and allergy. Treg transcriptional landscape is tightly controlled by Foxp3-binding partners, including RelA. Although those DNA-binding complexes have been well characterized, the TCR signaling events that coordinate those dynamic molecular assembly are still poorly understood. Using a combination of genetic models, we show that the suppressive function of Tregs is controlled by a tri-molecular interplay between the signaling proteins Themis1, Vav1 and SHP-1. We identify the tyrosine phosphatase SHP-1 as a central component of an inhibitory circuit, which leads to the dephosphorylation of Vav1, which in turn is associated with a dramatic reduction of RelA activity and Treg suppressive function. Themis1 disconnects this circuit by blocking SHP-1 catalytic activity. Collectively, our results reveal a previously unappreciated pathway, whereby Themis1-mediated repression of SHP-1 activity promotes Tregs suppressive functions through a Vav1-RelA signaling axis.
2021-06-01 | GSE165882 | GEO
Project description:Analysis of the transcriptional correlates of FOXP3 expression in suppressive and non-suppressive primary human Treg cell clones. Individual CD4+CD25High or Cd4+CD25- T cells were isolated from human PBMCs and expanded in vitro. After 3 weeks of expansion, individual clones were analysed for FOXP3 expression and in vitro suppressive activity against freshly sorted allogeneic effector T cells. This study analyses the total RNA isolated from FOXP3+ clones with suppressive potency to their non-suppressive counterparts. The resutls of this study should provide insights into the molecular pathways linking FOXP3 expression to distinct aspects of Treg phenotype and function. Total RNA obtained from individual clones of primary human regulatory and effector CD4+T cells.
2015-05-06 | E-GEOD-65650 | biostudies-arrayexpress
Project description:Regulatory T (Treg) cells actively control pathological immune responses and immunotherapeutic strategies triggering an increase in the number and/or the function of endogenous Treg cells emerge as a promising therapeutic strategy in autoimmune diseases to restore tolerance. A remarkable heterogeneity in peripheral Treg cells has been evidenced and underscored the need to better characterize them and compare their suppressive function to determine which Treg subset will be optimally suitable for a given clinical situation. We demonstrated that repetitive injections of immature dendritic cells (DC) expand FoxP3-negative CD49b+ Treg cells that display an effector memory phenotype. Transcriptome analysis of ex-vivo isolated Treg-expanded by DC injections contains multiple transcripts of the canonical Treg signature shared mainly by CD25+ but also by other Treg subphenotypes. We provided an in-depth characterization of the CD49b+ Treg cells phenotype underscoring their similarities with CD25+ Treg cells and highlighting some specific expression pattern for several markers including LAG3, KLRG1, CD103, ICOS, CTLA-4 and GZB. Comparison of their suppressive mechanism in vitro and in vivo with that of FoxP3-positive Treg cells provide evidence of their potent suppressive activity in vivo, partly dependent on IL-10 secretion. Altogether our results underscore the therapeutic potential of IL-10 secreting CD49b+ Treg cells in arthritis and strongly suggest that expression of several canonical markers and suppressive function could be FoxP3-independent All gene expression profiles were obtained from highly purified T cell populations sorted by flow cytometry. To reduce variability, cells from multiple mice were pooled for sorting, and two to three replicates were generated for all groups. RNA from 2.5-10 x 105 cells was amplified, labeled, and hybridized to Affymetrix M430v2 microarrays.
2015-12-10 | E-GEOD-68621 | biostudies-arrayexpress
Project description:The NOD (nonobese diabetic) mouse strain develops a characteristic autoimmune syndrome that closely resembles human type I diabetes. It has been suggested that NOD mice exhibit both numerical deficiency in CD4+CD25+ regulatory T cells (Treg) and reduced suppressive activity. We compared sorted CD4+CD25+ Tregs from the spleens of 6-7 week-old female NOD and nondiabetic B6.H2g7 mice. Tregs were 93±2% and 95±1% Foxp3+ in NOD and B6.H2g7 cells, respectively, on post-sort reanalysis. "Conventional" CD4+CD25- T cells (Tconv) are included as reference populations. Surprisingly, Treg "signature" is similar between the two strains, with only a few probesets that subtly deviate. Keywords: Cell population comparison from two mouse strains. For each strain (NOD and B6.g7), we analyzed two populations: CD4+CD25+ Treg and CD4+CD25- Tconv cells, for a total of four distinct populations. RNA from three mice were pooled for each replicate; there are three independent replicates for each population. After RMA normalization, intensity values were averaged across the three replicates and analyzed. We calculated the ratio of Treg/Tconv intensity values for each strain and compared the results.
2008-12-19 | E-GEOD-6813 | biostudies-arrayexpress
Project description:Regulatory T (Treg) cells actively control pathological immune responses and immunotherapeutic strategies triggering an increase in the number and/or the function of endogenous Treg cells emerge as a promising therapeutic strategy in autoimmune diseases to restore tolerance. A remarkable heterogeneity in peripheral Treg cells has been evidenced and underscored the need to better characterize them and compare their suppressive function to determine which Treg subset will be optimally suitable for a given clinical situation. We demonstrated that repetitive injections of immature dendritic cells (DC) expand FoxP3-negative CD49b+ Treg cells that display an effector memory phenotype. Transcriptome analysis of ex-vivo isolated Treg-expanded by DC injections contains multiple transcripts of the canonical Treg signature shared mainly by CD25+ but also by other Treg subphenotypes. We provided an in-depth characterization of the CD49b+ Treg cells phenotype underscoring their similarities with CD25+ Treg cells and highlighting some specific expression pattern for several markers including LAG3, KLRG1, CD103, ICOS, CTLA-4 and GZB. Comparison of their suppressive mechanism in vitro and in vivo with that of FoxP3-positive Treg cells provide evidence of their potent suppressive activity in vivo, partly dependent on IL-10 secretion. Altogether our results underscore the therapeutic potential of IL-10 secreting CD49b+ Treg cells in arthritis and strongly suggest that expression of several canonical markers and suppressive function could be FoxP3-independent
2015-12-10 | GSE68621 | GEO
Project description:Analysis of the transcriptional correlates of FOXP3 expression in suppressive and non-suppressive primary human Treg cell clones. Individual CD4+CD25High or Cd4+CD25- T cells were isolated from human PBMCs and expanded in vitro. After 3 weeks of expansion, individual clones were analysed for FOXP3 expression and in vitro suppressive activity against freshly sorted allogeneic effector T cells. This study analyses the total RNA isolated from FOXP3+ clones with suppressive potency to their non-suppressive counterparts. The resutls of this study should provide insights into the molecular pathways linking FOXP3 expression to distinct aspects of Treg phenotype and function.
2015-05-06 | GSE65650 | GEO