bach2

Human Inborn Errors of Immunity (IEIs) encompass a clinically and genetically heterogeneous group of disorders, ranging from mild cases to severe, life-threatening types. Among these, Primary Immune Regulatory Disorders (PIRDs) constitute a subset of IEIs characterized by diverse clinical phenotypes, prominently featuring severe atopy, autoimmunity, lymphoproliferation, hyperinflammation, autoinflammation, and susceptibility to malignancies. According to the latest report from the International Union of Immunological Societies (IUIS), PIRDs arise from mutations in various genes including LYST, RAB27A, AP3B1, AP3D1, PRF1, UNC13D, STX11, STXBP2, FAAP24, SLC7A7, RASGRP1, CD70, CTPS1, RLTPR, ITK, MAGT1, PRKCD, TNFRSF9, SH2DIA, XIAP, CD27 (TNFRSF7), FAS (TNFRSF6), FASLG (TNFSF6), CASP10, CASP8, FADD, LRBA, STAT3, AIRE, ITCH, ZAP70, TPP2, JAK1, PEPD, FOXP3, IL2RA, CTLA4, BACH2, IL2RB, DEF6, FERMT1, IL10, IL10RA, IL10RB, NFAT5, TGFB1, and RIPK1 genes...

Epstein-Barr virus (EBV) is an important cause of human lymphomas, including Burkitt lymphoma (BL). EBV+ BLs are driven by Myc translocation and have stringent forms of viral latency that do not express either of the two major EBV oncoproteins, EBNA2 (which mimics Notch signaling) and LMP1 (which activates NF-κB signaling). Suppression of Myc-induced apoptosis, often through mutation of the TP53 (p53) gene or inhibition of pro-apoptotic BCL2L11 (BIM) gene expression, is required for development of Myc-driven BLs...

Transcription factors BACH2 and IRF4 are both essential for antibody class-switch recombination (CSR) in activated B lymphocytes, while they oppositely regulate the differentiation of plasma cells (PCs). Here, we investigated how BACH2 and IRF4 interact during CSR and plasma-cell differentiation. We found that BACH2 organizes heterochromatin formation of target gene loci in mouse splenic B cells, including targets of IRF4 activation such as Aicda, an inducer of CSR, and Prdm1, a master plasma-cell regulator...

T cell exhaustion, which is observed in various chronic infections and malignancies, is characterized by elevated expression of multiple inhibitory receptors, impaired effector functions, decreased proliferation, and reduced cytokine production. Notably, while adoptive T cell therapies, such as chimeric antigen receptor (CAR)-T therapy, have shown promise in treating cancer and other diseases, the efficacy of these therapies is often compromised by T cell exhaustion. It is imperative, therefore, to understand the mechanisms underlying this exhaustion to promote advances in T cell-related therapies...

Aortic root aneurysm is a potentially life-threatening condition that may lead to aortic rupture and is often associated with genetic syndromes, such as Marfan syndrome (MFS). Although studies with MFS animal models have provided valuable insights into the pathogenesis of aortic root aneurysms, this understanding of the transcriptomic and epigenomic landscape in human aortic root tissue remains incomplete. This knowledge gap has impeded the development of effective targeted therapies. Here, this study performs the first integrative analysis of single-nucleus multiomic (gene expression and chromatin accessibility) and spatial transcriptomic sequencing data of human aortic root tissue under healthy and MFS conditions...

Bach2 was initially discovered in B cells, where it was revealed to control the transcription involved in cell differentiation. Bach2 is intimately connected to CD8 + T lymphocytes in various differentiation states and subsets according to recent findings. Bach2 can regulate primitive T cells, stimulate the development and differentiation of memory CD8 + T cells, inhibit the differentiation of effector CD8 + T cells, and play a significant role in the exhaustion of CD8 + T cells...

Studies have shown that a series of molecular events caused by oxidative stress is associated with ferroptosis and oxidation after ischemic stroke (IS). Differential analysis was performed to identify differentially expressed mRNA (DEmRNAs) between IS and control groups. Critical module genes were identified using weighted gene co-expression network analysis (WGCNA). DEmRNAs, critical module genes, oxidative stress-related genes (ORGs), and ferroptosis-related genes (FRGs) were crossed to screen for intersection mRNAs...

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive subtype of ALL characterized by its high heterogeneity and unfavorable clinical features. Despite improved insights in genetic and epigenetic landscapes of T-ALL, the molecular mechanisms that drive malignant T-cell development remain unclear. BTB and CNC homology 2 (BACH2) is a lymphoid-specific transcription repressor recognized as a tumor suppressor in B-cell malignancies, but little is known about its function and regulatory network in T-ALL. Here we found extremely low levels of BACH2 in T-ALL clinical samples and cell lines compared to normal T cells...

BACKGROUND: Machine learning (ML) has emerged as a vital asset for researchers to analyze and extract valuable information from complex datasets. However, developing an effective and robust ML pipeline can present a real challenge, demanding considerable time and effort, thereby impeding research progress. Existing tools in this landscape require a profound understanding of ML principles and programming skills. Furthermore, users are required to engage in the comprehensive configuration of their ML pipeline to obtain optimal performance...

Interferon regulatory factor 4 (IRF4) is a master transcription factor that regulates T helper cell (Th) differentiation. It interacts with the Basic leucine zipper transcription factor, ATF-like (BATF), depletion of which in CD4+ T cells abrogates acute graft-versus-host disease (aGVHD)-induced colitis. Here, we investigated the immune-regulatory role of Irf4 in a mouse model of MHC-mismatched bone marrow transplantation. We found that recipients of allogenic Irf4 -/- CD4+ T cells developed less GVHD-related symptoms...

Stem-like T cell populations can selectively promote autoimmunity, but the activities that sustain these populations are incompletely understood. Here, we show that T cell-intrinsic loss of the transcription cofactor OCA-B protects mice from experimental autoimmune encephalomyelitis (EAE) while preserving responses to infection. In EAE models driven by antigen re-encounter, OCA-B deletion eliminates CNS infiltration, proinflammatory cytokine production and clinical disease. OCA-B-expressing CD4 + T cells within the CNS of mice with EAE display a memory phenotype and preferentially confer disease...

Older age is one of the most important shared risk factors for multiple chronic diseases, increasing the medical burden to contemporary societies. Current research focuses on identifying aging biomarkers to predict aging trajectories and developing interventions aimed at preventing and delaying the progression of multimorbidity with aging. Here, a transcriptomic changes analysis of whole blood genes with age was conducted. The age-related whole blood gene-expression profiling datasets were downloaded from the Gene Expression Omnibus (GEO) database...

The underlying genetic susceptibility for Alzheimer's disease (AD) is not yet fully understood. The heterogeneous nature of the disease challenges genetic association studies. Endophenotype approaches can help to address this challenge by more direct interrogation of biological traits related to the disease. AD endophenotypes based on amyloid-β, tau, and neurodegeneration (A/T/N) biomarkers and cognitive performance were selected from the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort (N = 1565)...

Generation of memory B cells is one of the key features of adaptive immunity as they respond rapidly to re-exposure to the antigen and generate functional antibodies. Although the functions of memory B cells are becoming clearer, the regulation of memory B cell generation and maintenance is still not well understood. Here we found that transcription factor SpiB is expressed in some germinal center (GC) B cells and memory B cells and participates in the maintenance of memory B cells. Overexpression and knockdown analyses revealed that SpiB suppresses plasma cell differentiation by suppressing the expression of Blimp1 while inducing Bach2 in the in-vitro -induced germinal center B (iGB) cell culture system, and that SpiB facilitates in-vivo appearance of memory-like B cells derived from the iGB cells...

CXCR5 is a hallmark of T follicular helper (Tfh) cells. The mechanism of CXCR5 induction, however, is still incompletely understood. In this study, we report that in mice with the absence of transcription factor Bach2, the Th17-inducing cytokines IL-6 and TGF-β together induced CXCR5 expression in vitro. Mechanistically, IL-6/STAT3 drove Cxcr5 promoter activity via the upstream site 1 regulatory element, whereas TGF-β enhanced permissive histone modifications, and the STAT3 binding to the site 1 regulatory element was higher in the absence of Bach2...

The differentiation of naive CD8+ T lymphocytes into cytotoxic effector and memory CTL results in large-scale changes in transcriptional and phenotypic profiles. Little is known about how large-scale changes in genome organization underpin these transcriptional programs. We use Hi-C to map changes in the spatial organization of long-range genome contacts within naive, effector, and memory virus-specific CD8+ T cells. We observe that the architecture of the naive CD8+ T cell genome is distinct from effector and memory genome configurations, with extensive changes within discrete functional chromatin domains associated with effector/memory differentiation...

BACKGROUND: This study aims to explore the potential mechanism of action of the newly discovered hsa_circ_0128899 (circSPEF2) in diffuse large B-cell lymphoma (DLBCL). METHODS: circSPEF2, miR-16-5p and BTB and CNC homologue 2 (BACH2) expression patterns in DLBCL patients and cell lines were studied by RT-qPCR. The biological function of circSPEF2 in vitro and in vivo was investigated by function acquisition experiments. The proliferation activity of lymphoma cells was detected by MTT...

Epstein-Barr virus (EBV) and Plasmodium falciparum have a well described role in the development of endemic Burkitt lymphoma (BL), yet the mechanisms involved remain unknown. A major hallmark of malarial disease is hemolysis and bystander eryptosis of red blood cells, which causes release of free heme in large quantities into peripheral blood. We hypothesized that heme released during malaria infection drives differentiation of latently infected EBV-positive B cells, resulting in viral reactivation and release of infectious virus...

The Group ACYW135 meningococcal polysaccharide vaccine (MPV-ACYW135) is a classical common vaccine used to prevent Neisseria meningitidis serogroups A, C, Y, and W135, but studies on the vaccine at the transcriptional level are still limited. In the present study, mRNAs and lncRNAs related to immunity were screened from the spleens of mice inoculated with MPV-ACYW135 and compared with the control group to identify differentially expressed mRNAs and lncRNAs in the immune response. The result revealed 34375 lncRNAs and 41321 mRNAs, including 405 differentially expressed (DE) lncRNAs and 52 DE mRNAs between the MPV group and the control group...

Ferroptosis is a predominant contributor to renal ischemia reperfusion injury (IRI) after kidney transplant, evoking delayed graft function and poorer long-term outcomes. The wide propagation of ferroptosis among cell populations in a wave-like manner, developing the "wave of ferroptosis" causes a larger area of tubular necrosis and accordingly aggravates renal allograft IRI. In this study, we decipher a whole new metabolic mechanism underlying ferroptosis and propose a novel spreading pathway of the "wave of ferroptosis" in the renal tissue microenvironment, in which renal IRI cell-secreted small extracellular vesicles (IRI-sEVs) delivering lncRNA WAC-AS1 reprogram glucose metabolism in adjacent renal tubular epithelial cell populations by inducing GFPT1 expression and increasing hexosamine biosynthesis pathway (HBP) flux, and consequently enhances O-GlcNAcylation...