Comparison of Splenic Nrp1- and Nrp1+ Treg Populations
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ABSTRACT:
ORGANISM(S): Mus musculus
SUBMITTER: Jonathan Weiss
PROVIDER: E-GEOD-40441 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:To compare subpopulations of Treg cells in wild type mice based upon Nrp1 Expression, differentiating nTreg and iTreg
2012-08-30 | GSE40441 | GEO
Project description:This SuperSeries is composed of the following subset Series: GSE40441: Comparison of Splenic Nrp1- and Nrp1+ Treg Populations GSE40443: iTreg cells compared to WT Total Treg Refer to individual Series
2012-08-30 | E-GEOD-40488 | biostudies-arrayexpress
Project description:iTreg cells from Tbmc mLN mice treated with one week of 1% Oral Ova were compared to Total Treg from WT mice. Tbmc mice were treated with 1% Oral Ova and Foxp3 GFP+ CD4+ cells were sorted from mLN. CD4+ Foxp3+ cells were also sorted from WT Foxp3 GFP Balb/c mice.
2012-08-30 | E-GEOD-40443 | biostudies-arrayexpress
Project description:The relative contribution of induced and natural Foxp3+ regulatory T cells (iTreg and nTreg cells, respectively) to the maintenance of tolerance is unknown. We examined their respective roles by in vivo adoptive transfer immunotherapy of newborn Foxp3-deficient BALB/c mice. Survival, weight gain, tissue infiltration, T cell activation, and the concentration of proinflammatory cytokines were used as outcome measurements. Treatment with iTreg cells alone was not successful. While effective in preventing death, treatment with nTreg cells alone was associated with chronic inflammation and autoimmunity. Outcomes markedly improved when conventional T (Tconv) cells were transferred together with the nTreg cells, where 10% of the peripheral Treg cell pool was derived by in-situ conversion. This enhancement depended upon the capacity of Tconv cells to express Foxp3. The gene expression profile of in vivo derived iTreg cells was similar to the established nTreg cell genetic signature. These results identify iTreg cells as an essential regulatory subset that supplements tolerance maintained by nTreg cells. Purified cells sorted by flow cytometry from 4-8 treated mice(pooled EGFP+ Thy1.1+ iTreg cells with that of EGFP+ Thy1.1+ nTreg cells sorted from the spleens and lymph nodes of treated mice) were used to generate total RNA for each iTreg and nTreg array set, which was labeled and hybridized to Affymetrix 430 2.0 GeneChips in accordance to the manufacturer’s protocol. Three 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 mice and b) in vitro derived iTreg cells 72 hours after Foxp3 induction, generated earlier. 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. Naïve CD4+EGFP– Tconv cells from Foxp3EGFP mice and in vitro derived iTreg cells 72 hours after Foxp3 induction datasets obtained from GSE14415: Naïve CD4+EGFP– Tconv cells from Foxp3EGFP mice: GSM360171 - GSM360173 In vitro derived iTreg cells 72 hours after Foxp3 induction: GSM360147 - GSM360151
2011-06-30 | E-GEOD-19512 | biostudies-arrayexpress
Project description:The relative contribution of induced and natural Foxp3+ regulatory T cells (iTreg and nTreg cells, respectively) to the maintenance of tolerance is unknown. We examined their respective roles by in vivo adoptive transfer immunotherapy of newborn Foxp3-deficient BALB/c mice. Survival, weight gain, tissue infiltration, T cell activation, and the concentration of proinflammatory cytokines were used as outcome measurements. Treatment with iTreg cells alone was not successful. While effective in preventing death, treatment with nTreg cells alone was associated with chronic inflammation and autoimmunity. Outcomes markedly improved when conventional T (Tconv) cells were transferred together with the nTreg cells, where 10% of the peripheral Treg cell pool was derived by in-situ conversion. This enhancement depended upon the capacity of Tconv cells to express Foxp3. The gene expression profile of in vivo derived iTreg cells was similar to the established nTreg cell genetic signature. These results identify iTreg cells as an essential regulatory subset that supplements tolerance maintained by nTreg cells.
2011-06-30 | GSE19512 | GEO
Project description:Foxp3+ regulatory T cells (Treg), playing a crucial role in the maintenance of immune tolerance and prevention of autoimmune diseases, consist of thymus-derived naturally-occurring CD4+Foxp3+ Treg cells (nTreg) and another CD4+Foxp3+ Treg cells that can be induced ex vivo with TGF-β (iTreg). Although both Treg subsets share similar phenotypes and functional characteristics, they also have potential biologic differences on their biology. However, the role of iTreg in regulating B cells of lupus disease mice remains unclear so far. The lupus-prone New Zealand Mixed 2328 (NZM2328) mouse, a recombinant inbred strain that originated from the crosses among New Zealand Black and New Zealand White mice and their progenies also develops Lupus Glomerulonephritis. NZM2328 mice develop autoantibodies and glomerulonephritis with female predominance similarly to humans with systemic lupus erythematosus. The lupus disease onset is usually around 3-4 months age. In our experiments, iTreg induced from NZM2328 lupus-prone mice (10-12 weeks old) and nTreg sorted from the thymus of 10-12 weeks old NZM2328 lupus-prone mice were adoptively transferred into old NZM2328 mice (>4 months age) with established lupus for 32 days. Totally, there were three groups including NZM2328 mice as model (receive PBS), NZM2328 mice received iTreg, and NZM2328 received nTreg. The serum IgG and IgM autoantibody were detected by autoantibodies microarrays (UTSW Medical Center Autoantigen Array) at days 0, 14, 32 after cell transfer. Our results demonstrated that adoptive transfer of iTreg had a superior effect than nTreg subset on suppressing lupus B cell responses in vivo.
2017-01-26 | E-MTAB-4441 | 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: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.
2012-12-06 | GSE35543 | GEO
Project description:In order to identify if there is any role of Foxp1 in the DNA demethylation of Foxp3 enhancer regions of induced Treg (iTreg) cells we performed bisulfite sequence analysis of Foxp1 deficient in vitro generated iTreg cells and compared their methylation status after 7 days of iTreg induction, at which point Foxp1 is deleted in the iTreg cells derived from Foxp3YFPCreFoxp1f/f (KO) mice.
2018-10-02 | GSE118595 | GEO
Project description:Background: Regulatory T cells (Tregs) expressing the transcription factor FOXP3 are crucial mediators of self-tolerance, preventing autoimmune diseases but possibly hampering tumor rejection. Clinical manipulation of Tregs is of great interest, and first-in-man trials of Treg transfer achieved promising outcomes. Yet, the mechanisms governing induced Treg (iTreg) differentiation and the regulation of FOXP3 are incompletely understood. Results: To gain a comprehensive and unbiased molecular understanding of FOXP3 induction, we performed time-series RNA sequencing (RNA-Seq) and proteomics profiling on the same samples during human iTreg differentiation. To enable the broad analysis of universal FOXP3-inducing pathways, we used five differentiation protocols in parallel. Integrative analysis of the transcriptome and proteome confirmed involvement of specific molecular processes, as well as overlap of a novel iTreg subnetwork with known Treg regulators and autoimmunity-associated genes. Importantly, we propose 37 novel molecules putatively involved in iTreg differentiation. Their relevance was validated by: a targeted shRNA screen confirming a functional role in FOXP3 induction; discriminant analyses classifying iTregs accordingly; and comparable expression in an independent novel iTreg RNA Seq data set. Conclusion: The data generated by this novel approach facilitate understanding the molecular mechanisms underlying iTreg generation as well as the concomitant changes in the transcriptome and proteome. Our results provide a reference map exploitable for future discovery of markers and drug candidates governing control of Tregs, which has important implications for the treatment of cancer, autoimmune and inflammatory diseases
2018-04-06 | GSE96538 | GEO