Epigenetics in immune cells articles within Nature Communications

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  • Article
    | Open Access

    The epigenetic changes underlying the heterogeneity of RA disease presentation have been the subject of intense scrutiny. In this study, the authors use multiple single-cell sequencing datasets to define ‘chromatin superstates’ in patients with RA, which associate with distinct transcription factors and disease phenotypes.

    • Kathryn Weinand
    • , Saori Sakaue
    •  & Soumya Raychaudhuri

  • Article
    | Open Access

    The function of METTL3 and RNA methylation is important in various biological processes. Here the authors show that METTL3 is reduced in childhood asthma patients and that conditional knockout of Mettl3 in mouse myeloid cells enhances Th2 response and allergic asthma associated with changes in macrophage function.

    • Xiao Han
    • , Lijuan Liu
    •  & Yufeng Zhou

  • Article
    | Open Access

    Cell lineage specification involves substantial chromatin conformation reorganization. Here, the authors integrate in-situ Hi-C and PLAC-seq to map the dynamic changes in 3D chromatin structure during Treg cell differentiation. Furthermore, the authors further characterize the role of Foxp3 in the establishment of Treg-specific chromatin interactions by different Foxp3-mutant mouse lines.

    • Zhi Liu
    • , Dong-Sung Lee
    •  & Jesse R. Dixon

  • Article
    | Open Access

    The role of 3D genome organization is not well understood in the transcriptional regulation of dendritic cells. Here the authors show that activation of dendritic cells in vitro induces dynamic reprogramming of the chromatin looping and enhancer activity linked to changes in gene expression and implicates a role for the chromatin architecture protein CTCF in the inflammatory response of dendritic cells.

    • Bobae Yang
    • , Sueun Kim
    •  & Hyoung-Pyo Kim

  • Article
    | Open Access

    Th17 cells produce a range of characteristic Th17 type cytokines and express transcription factors governed by epigenetic regulation to engage the Th17 programme. Here the authors implicate the RNA 5- methylcytosine (m5C) methyltransferase Nsun2 in Th17 cells and the promotion of colitis in a murine model.

    • Wen-Lan Yang
    • , Weinan Qiu
    •  & Yun-Gui Yang

  • Article
    | Open Access

    Treg cells can be functionally altered by epigenetic modulators. Here the authors show that the histone H3K36 methyltransferase Setd2 is important for the survival of Treg cells and for the regulation of IL-33 mediated Th2 responses in mice and SETD2 expression is increased in Treg cells from human colorectal cancer tissue.

    • Zhaoyun Ding
    • , Ting Cai
    •  & Ju Qiu

  • Article
    | Open Access

    Lymph nodes in various locations of the body differ in their cell composition and gene expression signatures. Here authors show that the rapid postnatal expansion of lymph nodes is governed by CD34 + stromal cells and fibroblastic reticular stromal cell progenitors, distinguished by intrinsic, microbiome-independent core epigenetic blueprints.

    • Joern Pezoldt
    • , Carolin Wiechers
    •  & Jochen Huehn

  • Article
    | Open Access

    The UCLA Ribonomics group reports that the nuclear export efficiency of innate immune mRNAs varies over a hundred-fold range such that for many genes only a small fraction of the newly synthesized premRNA reaches the cytoplasm. They show that nuclear export and cytoplasmic decay rates are correlated thereby ensuring similar expression levels of short-lived and long-lived mRNAs.

    • Diane Lefaudeux
    • , Supriya Sen
    •  & Sri Kosuri

  • Article
    | Open Access

    Many studies assess epigenetic marks in white blood cells, but it is unclear how much immune factors affect the epigenome. Here, the authors show that fine-scale blood cell composition and cytomegalovirus infection affect the DNA methylome of adults.

    • Jacob Bergstedt
    • , Sadoune Ait Kaci Azzou
    •  & Lluis Quintana-Murci

  • Article
    | Open Access

    Epigenetic states that are established during thymic T cell development influence functionality of mature T cells. Authors here show that early developmental programming of the Cd4 locus is comprised of DNA-demethylation at a specific stimulus-responsive element, which allows long-term maintenance of activator histone H3K4 trimethylation and transcription.

    • Athmane Teghanemt
    • , Priyanjali Pulipati
    •  & Priya D. Issuree

  • Article
    | Open Access

    Integrating functional data with GWAS loci can help interpret the function of genetic variants associated with disease. Here the authors map cis and trans methylation QTL in CD4 + T cells from patients and colocalize with GWAS loci in order to interpret genetic variants associated with multiple sclerosis.

    • Tina Roostaei
    • , Hans-Ulrich Klein
    •  & Philip L. De Jager

  • Article
    | Open Access

    Macrophages employ epigenetic remodeling, especially the regulation of superenhancers (SEs), to promote classical polarization and function; whether liquid-liquid phase separation (LLPS) is involved is not known. Here, the authors show the epigenetic reader ZMYND8 forms condensates to deactivate latent SEs in a spatiotemporal manner and thereby restrict macrophage-mediated inflammation.

    • Pan Jia
    • , Xiang Li
    •  & Wei Lu

  • Article
    | Open Access

    Natural Killer cell development is controlled by two related transcription factors, Eomes and T-bet. Authors show here that while the two factors share a large proportion of their target genes, they regulate distinct developmental processes by differing in their pattern of expression and in their associated co-factors.

    • Jiang Zhang
    • , Stéphanie Le Gras
    •  & Thierry Walzer

  • Article
    | Open Access

    Development of the T cells requires functions from thymic epithelial cells, whose development and function are epigenetically regulated. Here the authors show that inactivation of the polycomb repressive complex 2 (PRC2) alters the H3K27me3 configuration, reduces TEC functions, reveals a specific TEC subset, and hampers T cell development.

    • Thomas Barthlott
    • , Adam E. Handel
    •  & Georg A. Holländer

  • Article
    | Open Access

    T regulatory (Treg) cells can differentiate into effector Treg (eTreg) cells that might be functional in inflammatory diseases. Using RNA sequencing and epigenetic profiling, the authors show that eTreg signatures in juvenile idiopathic arthritis joints are similar to tumour microenvironment (TME) Treg cells and are affected by tissue-specific epigenetic regulation.

    • Gerdien Mijnheer
    • , Lisanne Lutter
    •  & Femke van Wijk

  • Article
    | Open Access

    B cell progenitors differentiate into multiple subsets with distinct functions. Here the authors analyze the epigenetic landscapes of sorted B cell subsets using multiple platforms and show that the epigenetic regulator, DNMT3A, is essential for modulating the activity of enhancers critical for B1 and B2 lineage-determining genes.

    • Vinay S. Mahajan
    • , Hamid Mattoo
    •  & Shiv Pillai

  • Article
    | Open Access

    DNA methylation turnover is an essential epigenetic process during development. Here, the authors look at the changes in DNA methylation during the differentiation of post-mitotic human monocytes (MO), and find that EGR2 interacts with TET2 and is required for DNA demethylation at its binding sites; revealing EGR2 as an epigenetic pioneer factor in human MO.

    • Karina Mendes
    • , Sandra Schmidhofer
    •  & Michael Rehli

  • Article
    | Open Access

    N6-methyladenosine (m6A) is a reversible mRNA modification with important roles in cancer biology and immunoregulation. Here, the authors show that myeloid-specific deletion of Mettl3, the catalytic subunit of the methyltransferase complex, promotes tumor growth and metastasis in preclinical tumor models, influencing macrophage reprogramming and attenuating PD-1 blockade.

    • Huilong Yin
    • , Xiang Zhang
    •  & Rui Zhang

  • Article
    | Open Access

    During differentiation, chromosome conformation is remodelled to support lineage-specific transcriptional programs. Here, the authors characterise chromosome conformational changes in B lymphocytes as they differentiate into plasma cells, and provide evidence that chromosome reconfiguration occurs prior to DNA replication and mitosis and guides gene expression that controls differentiation.

    • Wing Fuk Chan
    • , Hannah D. Coughlan
    •  & Rhys S. Allan

  • Article
    | Open Access

    BATF is a transcription factor that is needed for IL-9 production by T helper 9 cells. Here the authors show that STAT5 is needed at the Il9 locus to enable BATF to function in this manner and that this interaction can reprogram other T helper subsets into IL-9 producing cells, thus regulating the immune response to disease.

    • Yongyao Fu
    • , Jocelyn Wang
    •  & Mark H. Kaplan

  • Article
    | Open Access

    The development of activated B cells into antibody-secreting cells (ASC) is a critical step for humoral immunity. Here the authors show, using adoptive transfers and single cell RNA sequencing, that commitment to ASC occurs soon following B cell activation, and is coordinated by specific transcriptome programs and proliferation kinetics.

    • Christopher D. Scharer
    • , Dillon G. Patterson
    •  & Jeremy M. Boss

  • Article
    | Open Access

    Whether the immune system aging differs between men and women is barely known. Here the authors characterize gene expression, chromatin state and immune subset composition in the blood of healthy humans 22 to 93 years of age, uncovering shared as well as sex-unique alterations, and create a web resource to interactively explore the data.

    • Eladio J. Márquez
    • , Cheng-han Chung
    •  & Duygu Ucar

  • Article
    | Open Access

    The transcription factor Bach2 is critical for T cell differentiation, but how it functions in Treg cells is unclear. Here the authors use a Treg-specific mouse model to show that Bach2 controls homeostasis and function of Treg cells by limiting DNA accessibility and activity of IRF4 in response to TCR signaling.

    • Tom Sidwell
    • , Yang Liao
    •  & Axel Kallies

  • Article
    | Open Access

    Sexual dimorphism is observed frequently in immune disorders, but the underlying insights are still unclear. Here the authors analyze transcriptome and epigenome changes induced by interferon in various mouse immune cell types, and find only a restricted set of sexual dimorphism genes in innate immunity and macrophages.

    • Shani Talia Gal-Oz
    • , Barbara Maier
    •  & Tal Shay

  • Article
    | Open Access

    Macrophage activation is synergistically controlled by lipopolysaccharide (LPS) and interferon-γ (IFN-γ). Here the authors show that IFN-γ promotes macrophage activation not only by activating STAT1-dependent genes, but also by suppressing STAT3-dependent negative feedback regulation downstream of LPS signaling.

    • Kyuho Kang
    • , Mahesh Bachu
    •  & Lionel B. Ivashkiv

  • Article
    | Open Access

    The authors show an important role for iron in B cell proliferation via histone 3 lysine 9 (H3K9) demethylation at the cyclin E1 promoter. Using a measles vaccination murine model, they show that iron-deficient individuals have a significantly reduced antibody response to the vaccine when compared to iron-normal controls.

    • Yuhang Jiang
    • , Cuifeng Li
    •  & Xiaoren Zhang

  • Article
    | Open Access

    Antibodies are generated through remote genomic interactions involving immunoglobulin variable (VH), diversity (DH) and joining (JH) gene segments. Here the authors develop a strategy to track VH-DHJH motion in B-lymphocytes and provide evidence that chromosome organisation near the sol-gel phase transition dictates the timing of genomic interactions to orchestrate gene expression and somatic recombination.

    • Nimish Khanna
    • , Yaojun Zhang
    •  & Cornelis Murre

  • Article
    | Open Access

    Autoreactive T cells are deleted in the thymus via thymic negative selection and Bim-mediated apoptosis. Here the authors identify a cis-acting enhancer, EBAB, that is essential for proper Bim expression and apoptosis induction, and show that EBAB deficiency specifically impairs thymic negative selection without affecting peripheral T cell homeostasis.

    • Miki Arai Hojo
    • , Kyoko Masuda
    •  & Shinpei Kawaoka

  • Article
    | Open Access

    The inability of T cells to properly mount anti-tumour immunity underlies failed cancer immune surveillance or therapy. Here the authors show that a microRNA, miR-155, suppresses Ship1 phosphatase expression to modulate epigenetic reprogramming of CD8 T cell differentiation via the Phf19/PRC2 axis, thereby implicating a novel aspect of cancer immunity regulation.

    • Yun Ji
    • , Jessica Fioravanti
    •  & Luca Gattinoni

  • Article
    | Open Access

    Loss of TET proteins in immune cell populations is known to result in immunopathology. Here the authors show that deficiency of Tet2 and Tet3 proteins, specifically in the CD4+ FoxP3+ Treg lineage, results in a dominant pathology in which ex-Treg cells and bystander T cells gain aberrant effector function.

    • Xiaojing Yue
    • , Chan-Wang J. Lio
    •  & Anjana Rao

  • Article
    | Open Access

    Here the authors examine how m6A modification is involved in innate immunity. They show that RNA methyltransferase Mettl3-mediated mRNA m6A methylation promotes dendritic cell (DC) activation and function, and in promoting DC-based T cells responses.

    • Huamin Wang
    • , Xiang Hu
    •  & Xuetao Cao

  • Article
    | Open Access

    Protective antibody responses depend critically on proper B cell development and differentiation at multiple stages. Here the authors show that a protein arginine methyltransferase, Prmt5 uses multiples pathways to prevent death of immature B cells, yet modulates, in p53-independent manners, the survival and differentiation of mature B cells.

    • Ludivine C. Litzler
    • , Astrid Zahn
    •  & Javier M. Di Noia

  • Article
    | Open Access

    Regulatory T (Treg) cells are developed in the thymus, and are essential for suppressing detrimental autoimmunity. Here the authors show, using mice with dampened interleukin 2 (IL-2) signaling, that IL-2 helps position the pioneer factor SATB1 to control genome-wide chromatin accessibility to facilitate Treg cell lineage commitment in the thymus.

    • Laurent Chorro
    • , Masako Suzuki
    •  & Grégoire Lauvau

  • Article
    | Open Access

    Interleukin-9 (IL-9) is important for allergy, autoimmunity and tumor immunity, but how its expression is regulated is unclear. Here the authors show the essential function of an enhancer, CNS-25 in mouse and CNS-18 in human, for IL-9 expression, with the deletion of this enhancer severely hampering IL-9 production in mice or human cells.

    • Byunghee Koh
    • , Amina Abdul Qayum
    •  & Mark H. Kaplan

  • Article
    | Open Access

    Interleukin-17 (IL-17)-secreting CD4 T cells (Th17) are induced by the master transcription factor RORγt, and are important for anti-fungal immunity and inflammatory responses. Here the authors show that Ubc9-mediated SUMOylation of RORγt induces HDAC2 binding to IL-17 promoter for suppressing IL-17 production in Th17 cells.

    • Amir Kumar Singh
    • , Prashant Khare
    •  & K. Venuprasad

  • Article
    | Open Access

    B-cell development is tightly regulated by transcription programs that are coordinated by transcription factors (TF) and locus accessibility. Here the authors show that, in mice and humans, the epigenetic reader BRWD1 inhibits and promotes the accessibility of enhancers for early and late B lymphopoiesis, respectively.

    • Malay Mandal
    • , Mark Maienschein-Cline
    •  & Marcus R. Clark

  • Article
    | Open Access

    The expression of CD4, a critical co-receptor providing T cell help in adaptive immunity, is finely tuned during development. Here the authors show that two enhancer elements, E4p and the newly-defined E4m, coordinate the expression and heritable demethylation of Cd4 in thymocytes but are dispensable for its sustained expression in peripheral T cells.

    • Priya D. Issuree
    • , Kenneth Day
    •  & Dan R. Littman

  • Article
    | Open Access

    Immunoglobulin E (IgE)-mediated food allergy is a major issue that affects 2–10% of infants. Here the authors study the epigenetic regulation of the naive CD4+ T cell activation response among children with IgE-mediated food allergy finding epigenetic dysregulation in the early stages of signal transduction through the T cell receptor complex.

    • David Martino
    • , Melanie Neeland
    •  & Richard Saffery

  • Article
    | Open Access

    Invariant natural killer T (iNKT) cells can be subsetted by their cytokine profiles, but how they develop in the thymus is unclear. Here the authors show, by analysing mice carrying mutant Zap70 genes, that T cell receptor signaling strength induces epigenetic changes of genes to modulate iNKT lineages.

    • Kathryn D. Tuttle
    • , S. Harsha Krovi
    •  & Laurent Gapin

  • Article
    | Open Access

    DNA methylation is known to contribute to B cell differentiation, but de novo methylation has not been studied in this context. Here the authors use a conditional Dnmt3a/b knockout mouse to map the function of de novo DNA methylation in B cell differentiation and the development of humoral immunity.

    • Benjamin G. Barwick
    • , Christopher D. Scharer
    •  & Jeremy M. Boss

  • Article
    | Open Access

    T help 17 (Th17) cells are important mediators for both protective and pathogenic immune reactions, but how their functions are regulated at the epigenetic level is not understood. Here the authors show that TRIM28, a cofactor for transcriptional regulation, is important for epigenetic activation of Th17-related gene loci during Th17 response.

    • Yu Jiang
    • , Ying Liu
    •  & Chen Dong

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