The transcription factor BATF is required for Th17 and TFH differentiation. Here, we show that BATF also has a fundamental role in regulating effector CD8+ T cell differentiation. BATF-deficient CD8+ T cells show profound defects in effector expansion and undergo proliferative and metabolic catastrophe early after antigen encounter. BATF, together with IRF4 and Jun proteins, binds to and promotes early expression of genes encoding lineage-specific transcription-factors (T-bet and Blimp-1) and cytokine receptors, while paradoxically repressing genes encoding effector molecules (IFNg and granzyme B). Thus, BATF amplifies TCR-dependent transcription factor expression and augments inflammatory signal propagation but restrains effector gene expression. This checkpoint prevents irreversible commitment to an effector fate until a critical threshold of downstream transcriptional activity has been achieved.
The transcription factor BATF operates as an essential differentiation checkpoint in early effector CD8+ T cells.
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XBP1 promotes triple-negative breast cancer by controlling the HIF1α pathway.
Specimen part, Cell line
View SamplesDuring cancer progression, carcinoma cells encounter a variety of cytotoxic stresses such as hypoxia, nutrient deprivation, and low pH as a result of inadequate vascularization. To maintain survival and growth in the face of these physiologic stressors, a set of adaptive response pathways are induced. One adaptive pathway well studied in other contexts is the unfolded protein response (UPR), of which XBP1 is an important component.
XBP1 promotes triple-negative breast cancer by controlling the HIF1α pathway.
Cell line
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Intersection of population variation and autoimmunity genetics in human T cell activation.
Sex, Age, Race, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Polarization of the effects of autoimmune and neurodegenerative risk alleles in leukocytes.
Sex, Age, Specimen part
View SamplesGene-expression microarray datasets generated as part of the Immunological Genome Project (ImmGen). Primary cells from multiple immune lineages are isolated ex-vivo, primarily from young adult B6 male mice, and double-sorted to >99% purity. RNA is extracted from cells in a centralized manner, amplified and hybridized to Affymetrix 1.0 ST MuGene arrays. Protocols are rigorously standardized for all sorting and RNA preparation. Data is released monthly in batches of cell populations.
Transcriptomes of the B and T lineages compared by multiplatform microarray profiling.
Sex, Age
View SamplesGene expression profiling of CD4 T-Cells (CD4+CD62L+) from human peripheral blood mononuclear cells (PBMCs). PBMCs were isolated from healthy individuals from the Boston area.
Polarization of the effects of autoimmune and neurodegenerative risk alleles in leukocytes.
Sex, Age, Specimen part
View SamplesGene expression profiling of Monocytes (CD14+CD16-) from human peripheral blood mononuclear cells (PBMCs). PBMCs were isolated from healthy individuals from the Boston area.
Polarization of the effects of autoimmune and neurodegenerative risk alleles in leukocytes.
Sex, Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Network pharmacology of JAK inhibitors.
Sex, Age, Specimen part, Compound
View SamplesSmall molecule inhibitors of JAK kinases have shown clinical effcacy in the treatment of certain autoimmune diseases. While these are known to block upstream JAK signalling events, their broader impact on the transcriptional footprint in immunocytes are unknown. Here we explore the effects of pan- and isoform-specific JAK blockade on the immuno-genomic network by genomic profiling.
Network pharmacology of JAK inhibitors.
Sex, Age, Specimen part, Compound
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