Gene regulation in immune cells articles within Nature Communications

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  • Article
    | Open Access

    Type 2 conventional dendritic cells (cDC2) are important immune activators in adults, but their development and functions at the neonatal stage remain unclear. Here the authors show, using fate-mapping and single-cell RNA sequencing, that neonatal cDC2 come from multiple origins, but converge functionally as potent immune activators upon proper stimuli.

    • Nikos E. Papaioannou
    • , Natallia Salei
    •  & Barbara U. Schraml

  • Article
    | Open Access

    Developing T cells commit to either CD4/helper or CD8/cytotoxic lineage in the thymus, but how CD4 and CD8 coreceptors and TCR signaling dictate this selection process is still unclear. Here the authors use single cell RNA sequencing of mouse thymocytes to show that, in selection intermediates, TCR signaling strength informs coreceptor expression timing.

    • Mohammad M. Karimi
    • , Ya Guo
    •  & Matthias Merkenschlager

  • Article
    | Open Access

    Innate-like T cells such as invariant natural killer T (iNKT) and mucosal-associated invariant T (MAIT) cells both develop in the thymus. Here the authors use single-cell RNA sequencing to show that mouse iNKT and MAIT share components of developmental regulation, with a transcription factor, Hivep3, implicated for the maturation of both cell types.

    • S. Harsha Krovi
    • , Jingjing Zhang
    •  & Laurent Gapin

  • Article
    | Open Access

    Here, the authors provide upper airway gene expression data from patients with COVID-19 and other viral and non-viral acute respiratory illnesses. They find attenuated activation of innate immune and pro-inflammatory pathways in COVID-19 as compared to other viral infections, which may contribute to its propensity for pre-symptomatic transmission.

    • Eran Mick
    • , Jack Kamm
    •  & Charles Langelier

  • 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

    Type 3 innate lymphoid cells (ILC3) are involved in maintaining gut immune homeostasis. Here the authors identify a circular RNA, circKcnt2, to be induced in ILC3s from inflamed gut, yet circKcnt2 deletion aggravates mouse experimental colitis, thereby implicating circKcnt2 as a potential feedback regulator of ILC3 activation and gut immunity.

    • Benyu Liu
    • , Buqing Ye
    •  & Zusen Fan

  • 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

    B cell development is tightly regulated in a stepwise manner to ensure proper generation of repertoire diversity via somatic gene rearrangements. Here, the authors show that a transcription factor, Erg, functions at the earliest stage to critically control two downstream factors, Ebf1 and Pax5, for modulating this gene rearrangement process.

    • Ashley P. Ng
    • , Hannah D. Coughlan
    •  & Warren S. Alexander

  • Article
    | Open Access

    Over 100 million of opioid prescriptions are issued yearly in the USA alone, but the impact of opioid use on the immune system is barely characterized. Here the authors report antiviral immune response is blunted in several types of blood cells from opioid-dependent individuals, and when healthy donor cells are exposed to morphine in a dish.

    • Tanya T. Karagiannis
    • , John P. Cleary Jr
    •  & Christine S. Cheng

  • Article
    | Open Access

    Macrophage activation is integral to innate immunity and inflammation, and involves transcriptome remodeling leading to the rapid upregulation of pro- and anti-inflammatory effector genes. Here the authors show that the negative elongation factor (NELF) complex controls the transcription of anti-inflammatory genes through Pol II pause release.

    • Li Yu
    • , Bin Zhang
    •  & Xiaoyu Hu

  • Article
    | Open Access

    Cytokines critically control the differentiation and functions of activated naïve and memory T cells. Here the authors show, using multi-omics and single-cell analyses, that naïve and memory T cells exhibit distinct cytokine responses, in which an ‘effectorness gradient’ is depicted by a transcriptional continuum, which shapes the downstream genetic programs.

    • Eddie Cano-Gamez
    • , Blagoje Soskic
    •  & Gosia Trynka

  • Article
    | Open Access

    CCL5 is an important chemokine for modulation of inflammatory responses, but how CCL5 expression is regulated is still unclear. Here the authors show that the CCL5 locus contains two enhancers, with the proximal enhancer being responsible for homeostatic expression and the distal enhancer enforcing inducibility, while both enhancers are modulated by RUNX3.

    • Wooseok Seo
    • , Kanako Shimizu
    •  & Ichiro Taniuchi

  • Article
    | Open Access

    Heterogeneous helper T (Th) cell responses contribute to differential susceptibility to immunological disorders. Here the authors perform haplotype-based computational screens of 16 inbred mouse strains to identify a transcription factor, p73, as an important negative regulator of Th1 differentiation, with p73 deficient mice manifesting alterations in two inflammatory disease models.

    • Min Ren
    • , Majid Kazemian
    •  & Warren J. Leonard

  • 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

    Langerhans cells (LC) can prime tolerogenic as well as immunogenic responses in the skin. Here the authors show, by transcriptomic, epigenetic and CRISPR editing analyses, that during LC migration and maturation the transcription factor IRF4 regulates expression of antigen presentation and co-stimulatory gene modules while attenuating inflammatory response genes.

    • Sofia Sirvent
    • , Andres F. Vallejo
    •  & Marta E. Polak

  • 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

    The ubiquitin ligase Siah2 has been implicated in immune responses. Here, the authors show that Siah2 null immune cells have an increased inflammatory response to inoculated melanoma cells, along with a reduced number of infiltrating immunosuppressive regulatory T cells, resulting in inhibition of tumour growth.

    • Marzia Scortegagna
    • , Kathryn Hockemeyer
    •  & Ze’ev A. Ronai

  • Article
    | Open Access

    Thymic epithelial cells (TEC) are essential for the maturation of functional T cells, while thymus size is proportional to the overall output efficiency. Here the authors show, using transcriptome analyses, that mouse fetal TEC maintain a Myc-dependent genetic program to ensure a rapid increase in thymus size, and thereby expedited T cell generation.

    • Jennifer E. Cowan
    • , Justin Malin
    •  & Avinash Bhandoola

  • Article
    | Open Access

    Immune cells are shaped by the tissue environment, yet the states of healthy human T cells are mainly studied in the blood. Here, the authors perform single cell RNA-seq of T cells from tissues and blood of healthy donors and show its utility as a reference map for comparison of human T cell states in disease.

    • Peter A. Szabo
    • , Hanna Mendes Levitin
    •  & Peter A. Sims

  • Article
    | Open Access

    The master transcription factor RORγt, encoded by the RORC gene, controls the polarization of CD4+ T cells expressing interleukin-17 (Th17). Here the authors describe several regulatory elements at the RORC locus that are recognized by NFAT and NFkB to induce a permissive epigenetic configuration of the RORC gene for RORγt expression and Th17 differentiation.

    • Hanane Yahia-Cherbal
    • , Magda Rybczynska
    •  & Elisabetta Bianchi

  • Article
    | Open Access

    B cell response and antibody production are generally facilitated by CD4+ follicular helper (Tfh) cells. Here the authors identify a subset of CXCR5+PD1+CD8+ Tfh cells that is normally suppressed by STAT5 signaling, so that STAT5 deficiency in mice increases the number of these CD8+ Tfh cells and induces concomitant production of autoantibodies.

    • Yuhong Chen
    • , Mei Yu
    •  & Demin Wang

  • 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

    Natural killer (NK) cells are important innate immune cells with diverse functions. Here the authors use single-cell RNA-sequencing of purified human bone marrow and peripheral blood NK cells to define five populations of NK cells with distinct transcriptomic profile to further our understanding of NK development and heterogeneity.

    • Chao Yang
    • , Jason R. Siebert
    •  & Subramaniam Malarkannan

  • 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

    Bone marrow-derived monocytes are recruited to the gut to replenish the local macrophage pool. Here the authors show that, while such replenishment constitutively occur under homeostasis, gut inflammation induces an immediate, Trem1-related transcription change to recruited monocyte to enable a context-dependent modulation of macrophage functions.

    • Girmay Desalegn
    •  & Oliver Pabst

  • 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

    A rapid cellular response to interferons (IFNs) is critical for establishing antimicrobial immunity, but how cells switch from from homeostasis to IFN signaling is not fully understood. Here, the authors provide evidence that IFNs induce gene expression by alternating subunits of transcription factor ISGF3.

    • Ekaterini Platanitis
    • , Duygu Demiroz
    •  & Thomas Decker

  • Article
    | Open Access

    The authors present an extensive profile of host transcriptional respones to a diverse group of pathogens and allergens. In doing so, they identify TH1, type I IFN, TH17, and TH2 responses, that underlie each immune response in both the blood and lung, which represents a global profile of host-pathogen immune responses.

    • Akul Singhania
    • , Christine M. Graham
    •  & Anne O’Garra

  • 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

    Receptor tyrosine kinases localize to the cell surface and have been suggested to also have nuclear function. Here the authors provide evidence that Colony Stimulating Factor-1 Receptor (CSF-1R) migrates to the nucleus upon CSF-1 stimulation in monocytes and that upon differentiation into macrophages, CSF-1R localizes to TSS, co-localizes with H3K4me3, and interacts with ELK and YY1.

    • Laura Bencheikh
    • , M’Boyba Khadija Diop
    •  & Nathalie Droin

  • 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

    Regulatory T (Treg) cells are important for maintaining immune homeostasis. Here the authors show that STIM1 and STIM2, which activate the Ca2+ channel ORAI1, are essential for the differentiation of peripheral Treg cells into tissue-resident and follicular Treg cells and their ability to limit autoimmunity in mice.

    • Martin Vaeth
    • , Yin-Hu Wang
    •  & Stefan Feske

  • Article
    | Open Access

    Interleukin-2 (IL-2) signaling is required for regulatory T (Treg) cell differentiation in the thymus, but its function in peripheral Tregs is still unclear. Here the authors show, using inducible deletion of IL-2 receptor subunit CD25, that IL-2 signaling is essential for maintaining peripheral Treg homeostasis, but dispensable for lineage stability.

    • Kevin H. Toomer
    • , Jen Bon Lui
    •  & Thomas R. Malek

  • Article
    | Open Access

    In vitro differentiation of red blood cells (RBCs) is a desirable therapy for various disorders. Here the authors develop a culture system using stem cell-derived macrophages to show that inducible expression of a transcription factor, KLF1, enhances RBC production, potentially through the induction of three soluble factors, ANGPTL7, IL33 and SERPINB2.

    • Martha Lopez-Yrigoyen
    • , Cheng-Tao Yang
    •  & Lesley M. Forrester

  • Article
    | Open Access

    Long non-coding RNAs (lncRNA) constitute a large fraction of human transcriptome, and are reported, individually, for context-specific regulatory functions. Here the authors expand our understanding by providing a systemic, unbiased annotation of lncRNA to establish an atlas of lncRNA landscape during the induction of human humoral immune responses.

    • Xabier Agirre
    • , Cem Meydan
    •  & Ari Melnick

  • Article
    | Open Access

    Innate T cells (ITC) contain many subsets and are poised to promptly respond to antigens and pathogens, but how this poised state is maintained is still unclear. Here the authors perform single-cell RNA-seq to align the various ITC subsets along an ‘innateness gradient’ that is associated with changes in proliferation and effector functions.

    • Maria Gutierrez-Arcelus
    • , Nikola Teslovich
    •  & Patrick J. Brennan

  • Article
    | Open Access

    Group 2 innate lymphoid cells (ILC2) are important mediators for allergy, but how ILC2 are regulated under chronic inflammation is still unclear. Here the authors show that Runx transcription factors, which normally suppresses ILC2 activation at steady state, help promote ILC2 activation and type 2 cytokine production in lung allergy mouse models.

    • Chizuko Miyamoto
    • , Satoshi Kojo
    •  & Takashi Ebihara

  • 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

    Tr1 cells are considered an immunosuppressive CD4 T cell population producing IL-10. Here the authors show that IL-10 is insufficient for Tr1 immunosuppression, define surface markers and transcriptional program of the immunosuppressive subset within Tr1, and reveal its deficiency in patients with IBD.

    • Leonie Brockmann
    • , Shiwa Soukou
    •  & Samuel Huber

  • Article
    | Open Access

    Ezh2 is an histone methyltransferase that catalyzes H3K27me3. Here the authors show that Ezh2 promotes T follicular helper (TFH) differentiation and helper activity, by cooperating with Tcf1 to activate Bcl6 transcription and epigenetically repressing p19Arf, an antagonist of Bcl6 function and TFH cell survival.

    • Fengyin Li
    • , Zhouhao Zeng
    •  & Hai-Hui Xue

  • 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

    Invariant natural killer T (iNKT) cells rapidly enhance cytokine secretion and effector function following activation, but the underlying mechanism is still unclear. Here the authors show that an endoplasmic reticulum stress sensor, inositol-requiring enzyme 1α, activates the p38 kinase to stabilize cytokine mRNA for enhanced iNKT functions.

    • Srinath Govindarajan
    • , Djoere Gaublomme
    •  & Michael B. Drennan

  • Article
    | Open Access

    Regulatory T (Treg) cells need to be differentiated into effector Treg (eTreg), with the transcription factor IRF4 implicated during this process. Here the authors show that an AP-1 family transcription factor, JunB, is expressed in eTreg to promote the IRF4 transcription program, and regulate eTreg homeostasis and function.

    • Shin-ichi Koizumi
    • , Daiki Sasaki
    •  & Hiroki Ishikawa

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