Similar Datasets
Project description:Wild-Type vs BTP2 Treated Th1 and Pathogenic Th17 cells_ 96h
| PRJNA1210684 | ENA
Project description:We showed that the transcription factor Foxo3 played a specific role in the polarization of CD4+ T cells towards pathogenic Th1 cells producing both interferon-γ (IFN-γ) and granulocyte monocyte colony stimulating factor (GM-CSF). To understand the molecular mechanisms whereby Foxo3 controls CD4+ T cell differentiation, unbiased analysis of genes differentially expressed in Foxo3-deficient vs. Foxo3-sufficient CD4+ T cells was achieved using both resting and activated CD4+ T cells obtained following 12 or 24 hours of stimulation with anti-CD3 mAbs.
2016-09-01 | GSE86287 | GEO
Project description:CD4+ T cells differentiate into phenotypically distinct T-helper cells upon antigenic stimulation. Regulation of plasticity between these CD4+ T-cell lineages is critical for immune homeostasis and prevention of autoimmune diseases. However, the factors that regulate lineage stability are largely unknown. Here we investigate a role for retinoic acid (RA) in the regulation of lineage stability using T helper 1 (Th1) cells, traditionally considered the most phenotypically stable Th subset. We found that RA, through its receptor RARa, sustains stable expression of Th1 lineage specifying genes as well as repressing genes that instruct Th17 cell fate. RA signaling is essential for limiting Th1 cell conversion into Th17 effectors and for preventing pathogenic Th17 responses in vivo. Our studies identify RA-RARa as a key component of the regulatory network governing Th1 cell fate and define a new paradigm for the development of pathogenic Th17 cells. These findings have important implications for autoimmune diseases in which dysregulated Th1-Th17 responses are observed. IFN-gamma+ Th1 cells from IFNgeYFP reporter mouse; comparing dnRARa to WT
2015-03-10 | E-GEOD-60354 | biostudies-arrayexpress
Project description:Th17 cells have better stemness and differentiation potential, and under certain circumstances, they can be stimulated to differentiate into other subcelltypes including Th1 and Treg. Here, we report that compared to traditional Th1 and Th17 cells, Th17-derived Th1 cells had greater anti-tumor activity. Both C57 mice ACT therapy and CAR-T therapy models were used to validate it. Mechanism: Th17-derived Th1 cells are able to express Th1 effector molecules as well as retain a lower level of exhaustion than Th1 cells. Additionally, it has a higher amount of type 1 interferon response and a stronger capacity for migration. Our research offers a fresh perspective on how ACT therapy and CAR-T therapy might develop in the future.
2024-10-31 | GSE276409 | GEO
Project description:CD4+ T cells differentiate into phenotypically distinct T-helper cells upon antigenic stimulation. Regulation of plasticity between these CD4+ T-cell lineages is critical for immune homeostasis and prevention of autoimmune diseases. However, the factors that regulate lineage stability are largely unknown. Here we investigate a role for retinoic acid (RA) in the regulation of lineage stability using T helper 1 (Th1) cells, traditionally considered the most phenotypically stable Th subset. We found that RA, through its receptor RARa, sustains stable expression of Th1 lineage specifying genes as well as repressing genes that instruct Th17 cell fate. RA signaling is essential for limiting Th1 cell conversion into Th17 effectors and for preventing pathogenic Th17 responses in vivo. Our studies identify RA-RARa as a key component of the regulatory network governing Th1 cell fate and define a new paradigm for the development of pathogenic Th17 cells. These findings have important implications for autoimmune diseases in which dysregulated Th1-Th17 responses are observed. Identification of RARa binding in wild-type Th1 cells and mapping of enhancers using chromatin IP against p300, H3k4me1, H3k4me3, and H3k27ac in wild-type and dnRara Th1 cells.
2015-03-10 | E-GEOD-60353 | biostudies-arrayexpress
Project description:CD4+ T cells differentiate into phenotypically distinct T-helper cells upon antigenic stimulation. Regulation of plasticity between these CD4+ T-cell lineages is critical for immune homeostasis and prevention of autoimmune diseases. However, the factors that regulate lineage stability are largely unknown. Here we investigate a role for retinoic acid (RA) in the regulation of lineage stability using T helper 1 (Th1) cells, traditionally considered the most phenotypically stable Th subset. We found that RA, through its receptor RARa, sustains stable expression of Th1 lineage specifying genes as well as repressing genes that instruct Th17 cell fate. RA signaling is essential for limiting Th1 cell conversion into Th17 effectors and for preventing pathogenic Th17 responses in vivo. Our studies identify RA-RARa as a key component of the regulatory network governing Th1 cell fate and define a new paradigm for the development of pathogenic Th17 cells. These findings have important implications for autoimmune diseases in which dysregulated Th1-Th17 responses are observed.
2015-03-10 | GSE60355 | GEO
Project description:CD4+ T cells differentiate into phenotypically distinct T-helper cells upon antigenic stimulation. Regulation of plasticity between these CD4+ T-cell lineages is critical for immune homeostasis and prevention of autoimmune diseases. However, the factors that regulate lineage stability are largely unknown. Here we investigate a role for retinoic acid (RA) in the regulation of lineage stability using T helper 1 (Th1) cells, traditionally considered the most phenotypically stable Th subset. We found that RA, through its receptor RARa, sustains stable expression of Th1 lineage specifying genes as well as repressing genes that instruct Th17 cell fate. RA signaling is essential for limiting Th1 cell conversion into Th17 effectors and for preventing pathogenic Th17 responses in vivo. Our studies identify RA-RARa as a key component of the regulatory network governing Th1 cell fate and define a new paradigm for the development of pathogenic Th17 cells. These findings have important implications for autoimmune diseases in which dysregulated Th1-Th17 responses are observed.
2015-03-10 | GSE60354 | GEO
Project description:There is evidence that microglia interact with infiltrating Th1 and Th17 cells and this interaction results in mutual activation. However, the potential of a distinct cytokine milieu generated by these effector T cell subsets to activate microglia is poorly understood. In this study, we tested the ability of factors secreted by Th1 and Th17 cells to induce microglial activation. Interestingly, we found that only Th1-associated factors had the potential to activate microglia while the Th17-associated factors as well as direct contact of Th17 cells with microglia only had a minimal effect. Further Th1-derived factors triggered a proinflammatory M1-type gene expression profile in microglia Microglia harvested from mixed glial cultures were treated with supernatants from Th1- or Th17 cultures. Microglia cultured in medium was used as controls. At 16h post treatment RNA was isolated from the microglia and probed on Agilent´s murine 4x44k microarrays. RNA isolated from four independent experiments were used for the gene expression profiling. Microglia, Th1, Th17
2013-12-31 | E-GEOD-45384 | biostudies-arrayexpress
Project description:CD4+ T cells differentiate into phenotypically distinct T-helper cells upon antigenic stimulation. Regulation of plasticity between these CD4+ T-cell lineages is critical for immune homeostasis and prevention of autoimmune diseases. However, the factors that regulate lineage stability are largely unknown. Here we investigate a role for retinoic acid (RA) in the regulation of lineage stability using T helper 1 (Th1) cells, traditionally considered the most phenotypically stable Th subset. We found that RA, through its receptor RARa, sustains stable expression of Th1 lineage specifying genes as well as repressing genes that instruct Th17 cell fate. RA signaling is essential for limiting Th1 cell conversion into Th17 effectors and for preventing pathogenic Th17 responses in vivo. Our studies identify RA-RARa as a key component of the regulatory network governing Th1 cell fate and define a new paradigm for the development of pathogenic Th17 cells. These findings have important implications for autoimmune diseases in which dysregulated Th1-Th17 responses are observed.
2015-03-10 | GSE60353 | GEO
Project description:Rosacea is a common chronic inflammatory skin disease of unknown etiology. Our knowledge about an involvement of the adaptive immune system is very limited. We performed detailed transcriptome analysis, qRT-PCR, and quantitative immunohistochemistry on facial biopsies of rosacea patients, classified according to their clinical subtype. As controls, we used samples from healthy controls. Our study shows significant activation of the immune system in all subtypes of rosacea, characterizing erythematotelangiectatic rosacea (ETR) already as a disease with significant influx of proinflammatory cells. The T cell response is dominated by Th1/Th17-polarized immune cells, as demonstrated by significant upregulation of IFNγ or IL-17, for example. Chemokine expression patterns support a Th1/Th17 polarization profile of the T cell response. Macrophages and mast cells are increased in all three subtypes of rosacea, while neutrophils reach a maximum in papulopustular rosacea. Our studies also provide evidence for activation of plasma cells with significant antibody production already in ETR, followed by a crescendo pattern towards phymatous rosacea. In sum, Th1/Th17 polarized inflammation and macrophage infiltration is an underestimated hallmark in all subtypes of rosacea. Therapies directly targeting the Th1/Th17 pathway are promising candidates in the future treatment of this skin disease.
2015-06-01 | GSE65914 | GEO