Regulatory T cells (Treg cells) expressing the forkhead family transcription factor Foxp3 are critical mediators of dominant immune tolerance to self. Most Treg cells constitutively express the high-affinity interleukin 2 (IL-2) receptor alpha-chain (CD25); however, the precise function of IL-2 in Treg cell biology has remained controversial. To directly assess the effect of IL-2 signaling on Treg cell development and function, we analyzed mice containing the Foxp3gfp knock-in allele that were genetically deficient in either IL-2 (Il2-/-) or CD25 (Il2ra-/-). We found that IL-2 signaling was dispensable for the induction of Foxp3 expression in thymocytes from these mice, which indicated that IL-2 signaling does not have a nonredundant function in the development of Treg cells. Unexpectedly, Il2-/- and Il2ra-/- Treg cells were fully able to suppress T cell proliferation in vitro. In contrast, Foxp3 was not expressed in thymocytes or peripheral T cells from Il2rg-/- mice. Gene expression analysis showed that IL-2 signaling was required for maintenance of the expression of genes involved in the regulation of cell growth and metabolism. Thus, IL-2 signaling seems to be critically required for maintaining the homeostasis and competitive fitness of Treg cells in vivo.
A function for interleukin 2 in Foxp3-expressing regulatory T cells.
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View SamplesZXDC1 augments the expression of various markers of monocyte/macrophage differentiation when over-expressed in the U937 cell line treated with the phorbol ester PMA. Likewise, knockdown of ZXDC1 restricts the induced expression of these markers. We sought to identify specfic gene targets of ZXDC1 during the process of monocyte/macrophage differentiation in U937 by performing gene expression profiling in cells exhibiting reduced expression of ZXDC1 compared to controls.
The zinc finger transcription factor ZXDC activates CCL2 gene expression by opposing BCL6-mediated repression.
Specimen part, Cell line
View SamplesCombination therapy with estrogen and a selective estrogen receptor modulator (SERM) is a promising approach to safely alleviate important side effects related to estrogen deficiency in women at high risk for breast cancer. Data related to endometrial safety of estrogen+SERM co-therapies are limited, however. The primary goal of this study was to evaluate the endometrial profile of low-dose E2 and Tam alone and in combination.
Endometrial profile of tamoxifen and low-dose estradiol combination therapy.
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View SamplesExamination of CD4+ T cells from Foxp3-GFP knock-in mice. Aim is to understand the genetic program governed by Foxp3 in T cells by comparison of CD4 T cells subdivided into four groups based on expression of Foxp3 and CD25.
Regulatory T cell lineage specification by the forkhead transcription factor foxp3.
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View SamplesThis SuperSeries is composed of the SubSeries listed below.
Foxp3-dependent programme of regulatory T-cell differentiation.
Sex
View SamplesThe 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 932% and 951% 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.
The defect in T-cell regulation in NOD mice is an effect on the T-cell effectors.
Age, Specimen part
View SamplesThis data set is comprised of all peripheral (pooled lymph nodes and spleen) T cell subsets presented in this manuscript. These include T-N, T-25, T-FN and T-R cells; T-25, T-FN and T-R cells from mice treated with IL-2; and T-R cells transduced with empty, PDE3B-expressing or PDE3B(H801A)-expressing retroviral vectors (after transfer into recipient mice).
Foxp3-dependent programme of regulatory T-cell differentiation.
Sex
View SamplesThis data set is comprised of all thymic T cell subsets presented in this manuscript. These include T-N, T-25, T-FN and T-R thymocytes.
Foxp3-dependent programme of regulatory T-cell differentiation.
Sex
View SamplesRationale: Pulmonary arterial hypertension is a common and potentially fatal complication of scleroderma that may involve inflammatory and autoimmune mechanisms. Alterations in the gene expression of peripheral blood mononuclear cells have been previously described in patients with pulmonary arterial hypertension. The ability to identify patients at risk for developing pulmonary hypertension would be clinically beneficial.
Altered immune phenotype in peripheral blood cells of patients with scleroderma-associated pulmonary hypertension.
Sex, Specimen part, Disease, Disease stage
View SamplesDermal lymphatics form a network that connects all the hair follicles in skin and localize in proximity to the Hair Follicle Stem Cell. RNA sequencing analyses of isolated dermal lymphatics at two different time points of the hair follicle cycle (P55 and P70) indicate the existence of dynamic signaling networks associated with lymphatic remodeling, immune trafficking, and HF signaling. Overall design: Prox1CreERT2; ROSA26-LSL-eYFP mice of P55 (Mid Telogen) and P70 (Late telogen) were sacrificed and eYFP positive cells were isolated from the backskin.
Lymphatic vessels interact dynamically with the hair follicle stem cell niche during skin regeneration in vivo.
Treatment, Subject
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