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T Cell Fates Zipped Up: How the Bach2 Basic Leucine Zipper Transcriptional Repressor Directs T Cell Differentiation and Function.

ABSTRACT: Recent data illustrate a key role for the transcriptional regulator bric-a-brac, tramtrack, and broad complex and cap'n'collar homology (Bach)2 in orchestrating T cell differentiation and function. Although Bach2 has a well-described role in B cell differentiation, emerging data show that Bach2 is a prototypical member of a novel class of transcription factors that regulates transcriptional activity in T cells at super-enhancers, or regions of high transcriptional activity. Accumulating data demonstrate specific roles for Bach2 in favoring regulatory T cell generation, restraining effector T cell differentiation, and potentiating memory T cell development. Evidence suggests that Bach2 regulates various facets of T cell function by repressing other key transcriptional regulators such as B lymphocyte-induced maturation protein 1. In this review, we examine our present understanding of the role of Bach2 in T cell function and highlight the growing evidence that this transcriptional repressor functions as a key regulator involved in maintenance of T cell quiescence, T cell subset differentiation, and memory T cell generation.

SUBMITTER: Richer MJ

PROVIDER: S-EPMC4978142 | biostudies-other | 2016 Aug

REPOSITORIES: biostudies-other

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Project description:BackgroundBasic leucine zipper transcription factor (BATF) plays a crucial role in development and progression of different types of carcinomas. However, its prognostic value in kidney renal clear cell carcinoma (KIRC) is yet to be elucidated.MethodsWe obtained clinicopathological data and expression profiles of BATF from The Cancer Genome Atlas (TCGA) on the pan-cancer and KIRC perspectives. We calculated the area under the curve (AUC) of the receiver-operating characteristic curves to understand the discriminatory capacity of BATF. Next, we generated Kaplan-Meier curves to assess the effect of BATF on the overall survival (OS) of patients, then performed univariate and multivariate Cox regression analyses. Subsequently, we used multivariate regression to construct a nomogram for predicting prognosis. Furthermore, we construct a protein-protein interaction (PPI) network, then performed gene set enrichment and pathway enrichment analyses to determine the biological function of the co-expression genes. Finally, we performed tumor microenvironment analyses to establish the relationship between BATF expression and infiltrating immune cells.ResultsBATF was significantly upregulated in KIRC relative to normal kidney tissues. Upregulation of BATF mRNA was associated with higher TNM pathological stage, histological grade, and poor OS/PFI (progression-free interval). Receiver-operating characteristic (ROC) curves showed that BATF had excellent diagnostic value in KIRC, as evidenced by the AUC and cutoff values of 0.942 and 2.033, respectively. Kaplan-Meier survival curves demonstrated that KIRC patients with high-BATF were associated with worse prognosis (hazard ratio =1.42, P=0.024). Results from Cox univariate analyses indicated that BATF was an independent prognostic factor in KIRC patients, and survival probabilities were predicted by the established nomogram. Results from the Tumor Immune Estimation Resource (TIMER) and BATF mRNA expression showed an association with immune cell infiltration.ConclusionsBATF is a prognostic biomarker and a potential target for immune therapies in KIRC.

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T Cell Fates Zipped Up: How the Bach2 Basic Leucine Zipper Transcriptional Repressor Directs T Cell Differentiation and Function.

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