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  • Rewriting History: Epigenetic Reprogramming of CD8+ T Cell Differentiation to Enhance Immunotherapy
    Trends Immunol. (IF 13.422) Pub Date : 2020-07-02
    Caitlin C. Zebley; Stephen Gottschalk; Ben Youngblood

    The full potential of T cell-based immunotherapies remains limited by a variety of T cell extrinsic and intrinsic immunosuppressive mechanisms that can become imprinted to stably reduce the antitumor ability of T cells. Here, we discuss recent insights into memory CD8+ T cell differentiation and exhaustion and the association of these differentiation states with clinical outcomes during immune checkpoint

  • The Contribution of Epigenetics to Cancer Immunotherapy
    Trends Immunol. (IF 13.422) Pub Date : 2020-07-02
    Lorea Villanueva; Damiana Álvarez-Errico; Manel Esteller

    Effective anticancer immunotherapy treatments constitute a qualitative leap in cancer management. Nonetheless, not all patients benefit from such therapies because they fail to achieve complete responses, suffer frequent relapses, or develop potentially life-threatening toxicities. Epigenomic signatures in immune and cancer cells appear to be accurate and promising predictors of patient outcomes with

  • Flipping the Switch from Inflammation to Cell Death
    Trends Immunol. (IF 13.422) Pub Date : 2020-07-01
    Hayley I. Muendlein; Alexander Poltorak

    Multiple research groups have demonstrated that caspase-8 (CASP8)-mediated gasdermin D (GSDMD) cleavage drives pyroptotic cell death. Here, we discuss a novel role for the enzymatically inactive homolog of CASP8, the long isoform of cellular FLICE-like inhibitory protein (cFLIPL), in the regulation of this process. Specifically, cFLIP-deficiency provides a model in which to study the mechanisms regulating

  • Group 2 Innate Lymphoid Cells Induce Antibody Production in Gastric Tissue
    Trends Immunol. (IF 13.422) Pub Date : 2020-06-28
    Jennifer K. Bando; Marco Colonna

    A recent article published in Immunity by Naoko Satoh-Takayama et al. examines interactions between group 2 innate lymphocytes and gastric microbes that enhance IgA production.

  • Cardiac Mast Cells: Underappreciated Immune Cells in Cardiovascular Homeostasis and Disease
    Trends Immunol. (IF 13.422) Pub Date : 2020-06-28
    Gilda Varricchi; Gianni Marone; Petri T. Kovanen

    Mast cells are multifarious immune cells with complex roles in tissue homeostasis and disease. They produce a plethora of mediators that play roles in inflammation, angiogenesis, lymphangiogenesis, and tissue remodeling. Recent insights into the heterogeneity of cardiac mast cell (CMC) subpopulations have renewed interest in their functional diversity in homeostasis and disease. They are located within

  • Genetic Screening for Novel Regulators of Immune Checkpoint Molecules
    Trends Immunol. (IF 13.422) Pub Date : 2020-06-27
    Ramon Arens; Ferenc A. Scheeren

    Inhibitory and stimulatory immune checkpoint molecules play important roles in regulating immune responses. An increasing number of these immune regulators are currently being evaluated as targets in putative anti-cancer therapies. Recently, sophisticated genetic screens have been performed to increase our understanding of immune checkpoint pathways and their immunomodulatory regulators. Here, we summarize

  • Instructing Memory in CD8+ Thymocytes.
    Trends Immunol. (IF 13.422) Pub Date : 2020-06-06
    Katherine Maude Ashby,Kristin Ann Hogquist

    T cells can sometimes acquire properties of a memory cell without encountering foreign antigen. Miller et al. now show that development of such ‘memory phenotype’ (MP) CD8+ T cells starts with recognition of self-ligands in the thymus, and finishes in peripheral tissues. These cells respond rapidly during infection, and infiltrate tumors, where they express high amounts of PD-1.

  • Where There's Smoke, There's Fire: Inflammation Drives MDS.
    Trends Immunol. (IF 13.422) Pub Date : 2020-06-05
    Gandhar K Datar,Margaret A Goodell

    Chronic inflammation has been implicated in myelodysplastic syndrome (MDS); however, its role in disease progression is unclear. In a new study by Muto et al., MDS stem cells sparked with TRAF6-activated innate immune signaling were found to outcompete normal counterparts only when fueled by environmental inflammatory stimuli. Non-canonical NF-κB signaling is implicated in inflammatory synergy and

  • Origins of the RAG Transposome and the MHC.
    Trends Immunol. (IF 13.422) Pub Date : 2020-05-25
    Louis Tsakou-Ngouafo,Julien Paganini,Jim Kaufman,Pierre Pontarotti

    How innate immunity gave rise to adaptive immunity in vertebrates remains unknown. We propose an evolutionary scenario beginning with pathogen-associated molecular pattern(s) (PAMPs) being presented by molecule(s) on one cell to specific receptor(s) on other cells, much like MHC molecules and T cell receptors (TCRs). In this model, mutations in MHC-like molecule(s) that bound new PAMP(s) would not

  • The Speckled Protein (SP) Family: Immunity's Chromatin Readers.
    Trends Immunol. (IF 13.422) Pub Date : 2020-05-05
    Isabella Fraschilla,Kate L Jeffrey

    Chromatin ‘readers’ are central interpreters of the epigenome that facilitate cell-specific transcriptional programs and are therapeutic targets in cancer and inflammation. The Speckled Protein (SP) family of chromatin ‘readers’ in humans consists of SP100, SP110, SP140, and SP140L. SPs possess functional domains (SAND, PHD, bromodomain) that dock to DNA or post-translationally modified histones and

  • AID in Antibody Diversification: There and Back Again.
    Trends Immunol. (IF 13.422) Pub Date : 2020-04-27
    Yuqing Feng,Noé Seija,Javier M Di Noia,Alberto Martin

    Activation-Induced cytidine Deaminase (AID) initiates affinity maturation and isotype switching by deaminating deoxycytidines within immunoglobulin genes, leading to somatic hypermutation (SHM) and class switch recombination (CSR). AID thus potentiates the humoral response to clear pathogens. Marking the 20th anniversary of the discovery of AID, we review the current understanding of AID function.

  • Transcriptional Control of Mature B Cell Fates.
    Trends Immunol. (IF 13.422) Pub Date : 2020-05-20
    Hongsheng Wang,Herbert C Morse,Silvia Bolland

    The mature naïve B cell repertoire consists of three well-defined populations: B1, B2 (follicular B, FOB), and marginal zone B (MZB) cells. FOB cells are the dominant mature B cell population in the secondary lymphoid organs and blood of both humans and mice. The driving forces behind mature B lineage selection have been linked to B cell receptor (BCR) signaling strength and environmental cues, but

  • A Synchronous IRF4-Dependent Gene Regulatory Network in B and Helper T Cells Orchestrating the Antibody Response.
    Trends Immunol. (IF 13.422) Pub Date : 2020-05-25
    Sarah L Cook,Marissa C Franke,Evelyn P Sievert,Roger Sciammas

    Control of diverse pathogens requires an adaptive antibody response, dependent on cellular division of labor to allocate antigen-dependent B- and CD4+ T-cell fates that collaborate to control the quantity and quality of antibody. This is orchestrated by the dynamic action of key transcriptional regulators mediating gene expression programs in response to pathogen-specific environmental inputs. We describe

  • It Takes Three Receptors to Raise a B Cell.
    Trends Immunol. (IF 13.422) Pub Date : 2020-05-22
    Kaitlin C McLean,Malay Mandal

    As the unique source of diverse immunoglobulin repertoires, B lymphocytes are an indispensable part of humoral immunity. B cell progenitors progress through sequential and mutually exclusive states of proliferation and recombination, coordinated by cytokines and chemokines. Mutations affecting the crucial pre-B cell checkpoint result in immunodeficiency, autoimmunity, and leukemia. This checkpoint

  • A Future Outlook on Molecular Mechanisms of Immunity.
    Trends Immunol. (IF 13.422) Pub Date : 2020-06-02
    Amy S Weinmann,Ben A Youngblood,Stephen T Smale,Robert Brink,David G Schatz,Michael McHeyzer-Williams

  • Editorial: Moving Pieces in Molecular Immunology.
    Trends Immunol. (IF 13.422) Pub Date : 2020-05-13
    Catarina Sacristán

  • 'Rinse and Replace': Boosting T Cell Turnover To Reduce HIV-1 Reservoirs.
    Trends Immunol. (IF 13.422) Pub Date : 2020-05-12
    Zvi Grossman,Nevil J Singh,Francesco R Simonetti,Michael M Lederman,Daniel C Douek,Steven G Deeks,

    Latent HIV-1 persists indefinitely during antiretroviral therapy (ART) as an integrated silent genome in long-lived memory CD4+ T cells. In untreated infections, immune activation increases the turnover of intrinsically long-lived provirus-containing CD4+ T cells. Those are 'washed out' as a result of their activation, which when coupled to viral protein expression can facilitate local inflammation

  • Resident Memory T Cells Escape 'Home Quarantine'.
    Trends Immunol. (IF 13.422) Pub Date : 2020-05-06
    Marco Künzli,Carolyn G King

    T resident memory (Trm) cells provide a first line of defense in non-lymphoid tissues. A new report in Nature Immunology by Fonseca et al. reveals that CD8+ Trm cells can give rise to circulating effector and memory T cells, but remain predisposed to migrate back into their tissue of origin.

  • Opportunities for Small Molecules in Cancer Immunotherapy.
    Trends Immunol. (IF 13.422) Pub Date : 2020-05-04
    Sabina Y van der Zanden,Jolien J Luimstra,Jacques Neefjes,Jannie Borst,Huib Ovaa

    Cancer immunotherapy has proven remarkably successful through instigation of systemic antitumor T cell responses. Despite this achievement, further advancements are needed to expand the scope of susceptible cancer types and overcome variation in treatment outcomes between patients. Small-molecule drugs targeting defined pathways and/or cells capable of immune modulation are expected to substantially

  • Inflammation and Skeletal Muscle Regeneration: Leave It to the Macrophages!
    Trends Immunol. (IF 13.422) Pub Date : 2020-04-30
    Bénédicte Chazaud

    Inflammation is usually considered as harmful; however, it is also necessary for tissue recovery after injury. Macrophages exert immune and nonimmune functions throughout this process. During skeletal muscle regeneration, they mount an inflammatory response while exerting trophic roles on muscle and mesenchymal stem cells. Proinflammatory macrophages shift to being anti-inflammatory, triggering the

  • Circadian Influences of Diet on the Microbiome and Immunity.
    Trends Immunol. (IF 13.422) Pub Date : 2020-04-28
    Danping Zheng,Karina Ratiner,Eran Elinav

    Host circadian rhythmicity and the timing of feeding are increasingly recognized to cross-regulate and entrain each other, and may play crucial roles in regulating multiple physiological functions including host immunity and metabolic health. Of relevance, these circadian diet-immune interactions may be modulated by the gut microbiota. We review current knowledge linking the circadian clock and dietary

  • 更新日期:2020-04-24
  • ILC3s: Rhythmic Keepers of Gut Integrity at Mealtime.
    Trends Immunol. (IF 13.422) Pub Date : 2020-04-16
    Linda Quatrini,Lorenzo Moretta,Maria Cristina Mingari

    Cyclically, during the day, increased permeability of the intestinal epithelial barrier, allowing nutrient uptake, must be compensated for, to achieve increased protection against potentially harmful components. Seillet et al. demonstrate that, upon food intake, enteric neuron-derived VIP promotes anticipatory mucosal immunity by inducing ILC3s to produce protective IL-22.

  • An Antiviral DNA Response without the STING?
    Trends Immunol. (IF 13.422) Pub Date : 2020-04-15
    Katheryn Meek

    Higher eukaryotes have evolved elegant and redundant pathways to protect their genomes from both genotoxic stressors and foreign DNA from invading pathogens. Emerging data from Burleigh et al. suggest that these distinct pathways may share factors to enhance the functional redundancy of both.

  • How Neutrophils Meet Their End.
    Trends Immunol. (IF 13.422) Pub Date : 2020-04-14
    Shelley M Lawrence,Ross Corriden,Victor Nizet

    Neutrophil death can transpire via diverse pathways and is regulated by interactions with commensal and pathogenic microorganisms, environmental exposures, and cell age. At steady state, neutrophil turnover and replenishment are continually maintained via a delicate balance between host-mediated responses and microbial forces. Disruptions in this equilibrium directly impact neutrophil numbers in circulation

  • Remnant Epitopes Generating Autoimmunity: From Model to Useful Paradigm.
    Trends Immunol. (IF 13.422) Pub Date : 2020-04-13
    Ghislain Opdenakker,Ahmed Abu El-Asrar,Jo Van Damme

    Autoimmune diseases are defined as pathologies of adaptive immunity by the presence of autoantibodies or MHC-restricted autoantigen-reactive T cells. Because autoreactivity is a normal process based on mechanisms producing repertoires of antibodies and T cell receptors, crucial questions about disease mechanisms and key steps for interference have been outstanding. We defined 25 years ago the 'remnant

  • 更新日期:2020-04-11
  • Improving Vaccine-Induced Immunity: Can Baseline Predict Outcome?
    Trends Immunol. (IF 13.422) Pub Date : 2020-04-08
    John S Tsang,Carlota Dobaño,Pierre VanDamme,Gemma Moncunill,Arnaud Marchant,Rym Ben Othman,Manish Sadarangani,Wayne C Koff,Tobias R Kollmann

    Immune signatures measured at baseline and immediately prior to vaccination may predict the immune response to vaccination. Such pre-vaccine assessment might allow not only population-based, but also more personalized vaccination strategies ('precision vaccination'). If baseline immune signatures are predictive, the underlying mechanism they reflect may also determine vaccination outcome. Thus, baseline

  • Noncanonical Functions of Antibodies.
    Trends Immunol. (IF 13.422) Pub Date : 2020-04-06
    Jordan D Dimitrov,Sébastien Lacroix-Desmazes

    The typical functions of antibodies are based on linking the process of antigen recognition with initiation of innate immune reactions. With the introduction of modern research technologies and the use of sophisticated model systems, recent years have witnessed the discovery of a number of noncanonical functions of antibodies. These functions encompass either untypical strategies for neutralization

  • Breadth of Antibody Responses during Influenza Virus Infection and Vaccination.
    Trends Immunol. (IF 13.422) Pub Date : 2020-04-04
    Masato Kubo,Kosuke Miyauchi

    Influenza viruses are a major public health problem, causing severe respiratory diseases. Vaccines offer the effective protective strategy against influenza virus infection. However, the systemic and adaptive immune responses to infection and vaccination are quite different. Inactivated vaccines are the best available countermeasure to induce effective antibodies against the emerged virus, but the

  • Neutralizing Antibodies against SARS-CoV-2 and Other Human Coronaviruses.
    Trends Immunol. (IF 13.422) Pub Date : 2020-04-02
    Shibo Jiang,Christopher Hillyer,Lanying Du

    Coronavirus (CoV) disease 2019 (COVID-19) caused by severe acute respiratory syndrome (SARS)-CoV-2 (also known as 2019-nCoV) is threatening global public health, social stability, and economic development. To meet this challenge, this article discusses advances in the research and development of neutralizing antibodies (nAbs) for the prevention and treatment of infection by SARS-CoV-2 and other human

  • 'Nervous' Immunity: Walking the Tightrope.
    Trends Immunol. (IF 13.422) Pub Date : 2020-04-02
    Subhash Kulkarni,Sravya Kurapati,Milena Bogunovic

    There is a major gap in our understanding of how the intestinal immune and nervous systems are integrated to regulate protective adaptations to enteric infections while maintaining tissue homeostasis. Three recent complementary reports published in Cell (2020) provide new mechanistic insights into how this enteric neuro-immune crosstalk may occur.

  • A20 and Cell Death-driven Inflammation.
    Trends Immunol. (IF 13.422) Pub Date : 2020-03-30
    Dario Priem,Geert van Loo,Mathieu J M Bertrand

    A20 is a potent anti-inflammatory molecule, and mutations in TNFAIP3, the gene encoding A20, are associated with a wide panel of inflammatory pathologies, both in human and mouse. The anti-inflammatory properties of A20 are commonly attributed to its ability to suppress inflammatory NF-κB signaling by functioning as a ubiquitin-editing enzyme. However, A20 also protects cells from death, independently

  • Immunotherapeutic Potential of TGF-β Inhibition and Oncolytic Viruses.
    Trends Immunol. (IF 13.422) Pub Date : 2020-03-27
    Christianne Groeneveldt,Thorbald van Hall,Sjoerd H van der Burg,Peter Ten Dijke,Nadine van Montfoort

    In cancer immunotherapy, a patient's own immune system is harnessed against cancer. Immune checkpoint inhibitors release the brakes on tumor-reactive T cells and, therefore, are particularly effective in treating certain immune-infiltrated solid tumors. By contrast, solid tumors with immune-silent profiles show limited efficacy of checkpoint blockers due to several barriers. Recent discoveries highlight

  • Helper-like Innate Lymphoid Cells in Humans and Mice.
    Trends Immunol. (IF 13.422) Pub Date : 2020-03-26
    Sophie Guia,Emilie Narni-Mancinelli

    The innate lymphoid cell (ILC) family consists of natural killer (NK) cells, helper-like lymphoid cells (ILC1s, ILC2s, and ILC3s), and lymphoid tissue inducer (LTi) cells. Helper-like ILCs are considered the innate counterpart of T-helper cells because of similarities in their cytokine output and expression of key transcription factors. ILCs provide and regulate innate immune functions before the development

  • SARS Coronavirus Redux.
    Trends Immunol. (IF 13.422) Pub Date : 2020-03-12
    Enya Qing,Tom Gallagher

    As an atypical pneumonia began to appear in December 2019, Zhou et al. worked with remarkable speed to identify the associated virus, determine its relationship to animal viruses, and evaluate factors conferring infection susceptibility and resistance. These foundational results are being advanced to control the current worldwide human coronavirus epidemic.

  • Are You There? Genetic Variation Impacts Long-Distance Connections in Diabetes
    Trends Immunol. (IF 13.422) Pub Date : 2020-03-10
    Hannah C. Walter; Amy S. Weinmann

    A new study by Fasolino et al. defines how genetic variation in a mouse model of type 1 diabetes mellitus (T1DM) affects long-distance genomic interactions. The research has widespread implications for understanding how genetic diversity impacts disease susceptibility, and raises important concepts about mechanisms that can be influenced by genetic diversity between individuals.

  • Type IIA Secreted Phospholipase A2 in Host Defense against Bacterial Infections
    Trends Immunol. (IF 13.422) Pub Date : 2020-03-06
    Vincent P. van Hensbergen; Yongzheng Wu; Nina M. van Sorge; Lhousseine Touqui

    The enzyme type IIA secreted phospholipase A2 (sPLA2-IIA) is crucial for mammalian innate host defense against bacterial pathogens. Most studies have investigated the role of sPLA2-IIA in systemic bacterial infections, identifying molecular pathways of bacterial resistance against sPLA2-IIA-mediated killing, and providing insight into sPLA2-IIA mechanisms of action. Sensitization of (antibiotic-resistant)

  • Next-Generation Neuroimmunology: New Technologies to Understand Central Nervous System Autoimmunity
    Trends Immunol. (IF 13.422) Pub Date : 2020-03-05
    Gerd Meyer zu Hörste; Catharina C. Gross; Luisa Klotz; Nicholas Schwab; Heinz Wiendl

    Understanding neuroimmunological disorders is essential for developing new diagnostic and therapeutic strategies. Rodent models have provided valuable insights, but are sometimes equated with their human counterparts. Here, we summarize how novel technologies may enable an improved human-focused view of immune mechanisms. Recent studies have applied these new technologies to the brain parenchyma, its

  • Neuroimmune Connections in Aging and Neurodegenerative Diseases
    Trends Immunol. (IF 13.422) Pub Date : 2020-03-05
    Hannah Scheiblich; Melanie Trombly; Alfredo Ramirez; Michael T. Heneka

    In recent years, the inter-relationship between the innate immune system and the central nervous system (CNS) has moved to the forefront of biomedical research, with the discovery that these two physiological systems modulate each other by a steady mutual interaction. During normal brain aging, but also under certain pathological conditions, this crosstalk can go beyond physiological control, resulting

  • Sialoglycans and Siglecs Can Shape the Tumor Immune Microenvironment
    Trends Immunol. (IF 13.422) Pub Date : 2020-03-02
    Stephanie van de Wall; Kim C.M. Santegoets; Eline J.H. van Houtum; Christian Büll; Gosse J. Adema

    Sialic acid sugar-carrying glycans, sialoglycans, are aberrantly expressed on many tumor cells and have emerged as potent regulatory molecules involved in creating a tumor-supportive microenvironment. Sialoglycans can be recognized by sialic acid-binding immunoglobulin-like lectins (Siglecs), a family of immunomodulatory receptors. Most mammalian Siglecs transmit inhibitory signals comparable with

  • Deubiquitinases: Pro-oncogenic Activity and Therapeutic Targeting in Blood Malignancies.
    Trends Immunol. (IF 13.422) Pub Date : 2020-03-02
    Blanca T Gutierrez-Diaz,Wei Gu,Panagiotis Ntziachristos

    Deubiquitinases are enzymes that remove ubiquitin moieties from the vast majority of cellular proteins, controlling their stability, interactions, and localization. The expression and activity of deubiquitinases are critical for physiology and can go awry in various diseases, including cancer. Based on recent findings in human blood cancers, we discuss the functions of selected deubiquitinases in acute

  • The Fetal-Maternal Immune Interface in Uterus Transplantation.
    Trends Immunol. (IF 13.422) Pub Date : 2020-03-01
    Jasper Iske,Abdallah Elkhal,Stefan G Tullius

    Uterus transplants (UTxs) have been performed worldwide. Overall frequencies have been low, but globally initiated UTx programs are expected to increase clinical implementation. The uterus constitutes a unique immunological environment with specific features of tissue renewal and a receptive endometrium. Decidual immune cells facilitate embryo implantation and placenta development. Although UTx adds

  • Sarcoidosis and the mTOR, Rac1, and Autophagy Triad.
    Trends Immunol. (IF 13.422) Pub Date : 2020-02-28
    Yves Pacheco,Clarice X Lim,Thomas Weichhart,Dominique Valeyre,Abderrazzak Bentaher,Alain Calender

    Sarcoidosis is an enigmatic multisystem disease characterized by the development and accumulation of granulomas: a compact collection of macrophages that have differentiated into epithelioid cells and which are associated with T helper (Th)1 and Th17 cells. Although no single causative factor has been shown to underlie sarcoidosis in humans, its etiology has been related to microbial, environmental

  • CD38: Modulating Histone Methyltransferase EZH2 Activity in SLE.
    Trends Immunol. (IF 13.422) Pub Date : 2020-02-12
    Paramita Chakraborty,Shikhar Mehrotra

    To keep autoreactive T cells under control in SLE patients, immunosuppressive regimens are used, which can increase susceptibility to bacterial and viral infections. Recently, Katsuyama et al., demonstrated that the CD38/NAD/Sirtuin1/EZH2 axis reduces cytolytic CD8+ T cell function and might be targeted to overcome incidence of infections.

  • Maternal Leukocytes and Infant Immune Programming during Breastfeeding.
    Trends Immunol. (IF 13.422) Pub Date : 2020-02-10
    Amale Laouar

    The fetal immune system develops in a rather sterile environment relative to the outside world and, therefore, lacks antigenic education. Soon after birth, the newborn is exposed to the hostile environment of pathogens. Recently, animal- and limited human-based studies have indicated that help from the mother, upon transfer of leukocytes and their products via breast milk feeding, greatly assists the

  • Taking Insect Immunity to the Single-Cell Level.
    Trends Immunol. (IF 13.422) Pub Date : 2020-02-05
    Sarah Hélène Merkling,Louis Lambrechts

    For decades, insect immunology has contributed groundbreaking discoveries on the intricacies of innate immunity. These discoveries have profoundly impacted our understanding of innate immunology in mammalian systems and improved human therapeutic interventions, from the composition of vaccines to cell-based immune therapies. Current knowledge of insect immunity mainly encompasses detailed molecular

  • Arid5a, an RNA-Binding Protein in Immune Regulation: RNA Stability, Inflammation, and Autoimmunity.
    Trends Immunol. (IF 13.422) Pub Date : 2020-02-05
    Kishan Kumar Nyati,Mohammad Mahabub-Uz Zaman,Praveen Sharma,Tadamitsu Kishimoto

    AT-rich interactive domain 5A (ARID5A/Arid5a) is a known cofactor of transcription factors (TFs) that contributes to cell growth and differentiation. It has recently been recognized for its unique function in the stabilization of mRNA, which is associated with inflammatory autoimmune diseases. Studies have revolutionized our understanding of the post-transcriptional regulation of inflammatory genes

  • T Cell Co-stimulation and Functional Modulation by Innate Signals.
    Trends Immunol. (IF 13.422) Pub Date : 2020-02-05
    Takayuki Imanishi,Takashi Saito

    Pattern recognition receptors (PRRs), such as Toll-like receptors (TLRs), NOD-like receptors (NLRs), and RIG-I-like receptors (RLRs), play a pivotal role in the initiation of innate immune responses. Certain PRRs are also expressed by CD4+ and CD8+ T cells, where they function to provide co-stimulatory signals for their activation and differentiation. Recently, stimulator of interferon genes (STING)

  • Dynamic Post-Transcriptional Events Governing CD8+ T Cell Homeostasis and Effector Function.
    Trends Immunol. (IF 13.422) Pub Date : 2020-01-29
    Fiamma Salerno,Martin Turner,Monika C Wolkers

    Effective T cell responses against infections and tumors require a swift and ample production of cytokines, chemokines, and cytotoxic molecules. The production of these effector molecules relies on rapid changes of gene expression, determined by cell-intrinsic signals and environmental cues. Here, we review our current understanding of gene-specific regulatory networks that define the magnitude and

  • Nuclear Receptors in Cancer Inflammation and Immunity.
    Trends Immunol. (IF 13.422) Pub Date : 2020-01-22
    Linjie Zhao,Hongbo Hu,Jan-Åke Gustafsson,Shengtao Zhou

    Members of the nuclear receptor (NR) superfamily orchestrate cellular processes that can impact on numerous cancer hallmarks. NR activity plays important roles in the tumor microenvironment by controlling inflammation and immune responses. We summarize recent insights into the diverse mechanisms by which NR activity can control tumor inflammation, the roles of different NRs in modulating tumor immunity

  • Metabolic Adaptations to Infections at the Organismal Level.
    Trends Immunol. (IF 13.422) Pub Date : 2020-01-17
    Katia Troha,Janelle S Ayres

    Metabolic processes occurring during host-microbiota-pathogen interactions can favorably or negatively influence host survival during infection. Defining the metabolic needs of the three players, the mechanisms through which they acquire nutrients, and whether each participant cooperates or competes with each other to meet their own metabolic demands during infection has the potential to reveal new

  • Key Roles of MiT Transcription Factors in Innate Immunity and Inflammation.
    Trends Immunol. (IF 13.422) Pub Date : 2020-01-17
    Javier E Irazoqui

    Microphthalmia/TFE (MiT) transcription factors (TFs), such as transcription factor EB (TFEB) and transcription factor E3 (TFE3), are emerging as key regulators of innate immunity and inflammation. Rapid progress in the field requires a focused update on the latest advances. Recent studies show that TFEB and TFE3 function in innate immune cells to regulate antibacterial and antiviral responses downstream

  • Skin-Resident Innate Lymphoid Cells - Cutaneous Innate Guardians and Regulators.
    Trends Immunol. (IF 13.422) Pub Date : 2020-01-14
    Tetsuro Kobayashi,Roberto R Ricardo-Gonzalez,Kazuyo Moro

    Skin is the largest barrier organ and an important interface between the body and the outside environment. Immune surveillance and homeostatic regulation of skin function are governed by complex interactions between resident lymphoid and myeloid cells and their communications with the surrounding parenchyma. Recent studies have provided exciting insights about the unique characteristics of skin-resident

  • ACLY-matizing Macrophages to Histone Modification during Immunometabolic Reprogramming.
    Trends Immunol. (IF 13.422) Pub Date : 2020-01-13
    Niamh C Williams,Luke A O'Neill

    Metabolic reprogramming in macrophages supports effector functions and differs depending on the activating stimulus. Lauterbach et al. now show that early metabolic alterations in macrophages driven by LPS signaling serve to increase the acetyl-CoA pool via citrate metabolism by the ATP-citrate lyase (ACLY), leading to histone acetylation and regulation of TLR-driven gene expression.

  • Mitochondrial and Purinergic Dysregulation Promote Abnormal Behavior in Mice.
    Trends Immunol. (IF 13.422) Pub Date : 2020-01-13
    Ping Fang,Elaine Y Hsiao

    Increasing evidence implicates immune dysregulation in the development of neurological disorders. Recent research by Fan and colleagues deepens our understanding of how physical stress alters the immune system to promote anxiety-like behavior.

  • Control of Stimulus-Dependent Responses in Macrophages by SWI/SNF Chromatin Remodeling Complexes.
    Trends Immunol. (IF 13.422) Pub Date : 2020-01-09
    Jovylyn Gatchalian,Jingwen Liao,Matthew B Maxwell,Diana C Hargreaves

    Epigenetic regulation plays an important role in controlling the activation, timing, and resolution of innate immune responses in macrophages. Previously, SWI/SNF chromatin remodeling was found to define the kinetics and selectivity of gene activation in response to microbial ligands; however, these studies do not reflect a comprehensive understanding of SWI/SNF complex regulation. In 2018, a new variant

  • Human Secretory IgM: An Elusive Player in Mucosal Immunity.
    Trends Immunol. (IF 13.422) Pub Date : 2020-01-09
    Eva Michaud,Carmelo Mastrandrea,Nicolas Rochereau,Stéphane Paul

    Secretory IgMs (SIgMs) were amongst the first identified immunoglobulins. However, their importance was not fully understood and recent advances have shown they play a key role in establishing and promoting commensal gut tolerance in mice and humans. The true interactions between SIgMs and the microbiota remain controversial and we aim to consolidate current knowledge in this review. Through comprehensive

  • Stressed-Out T Cells Fragment the Mind.
    Trends Immunol. (IF 13.422) Pub Date : 2020-01-06
    Evan A Bordt,Staci D Bilbo

    The immune system is increasingly recognized to play an integral role in regulating stress responses. In a recent article in Cell, Fan et al. demonstrate a novel mechanism through which stress drives mitochondrial fragmentation-induced xanthine accumulation in mouse CD4+ T cells, subsequently acting on oligodendrocytes to induce anxiety-like behaviors.

  • From Loops to Looks: Transcription Factors and Chromatin Organization Shaping Terminal B Cell Differentiation.
    Trends Immunol. (IF 13.422) Pub Date : 2019-12-07
    Alba Azagra,Ester Marina-Zárate,Almudena R Ramiro,Biola M Javierre,Maribel Parra

    B lymphopoiesis is tightly regulated at the level of gene transcription. In recent years, investigators have shed light on the transcription factor networks and the epigenetic machinery involved at all differentiation steps of mammalian B cell development. During terminal differentiation, B cells undergo dramatic changes in gene transcriptional programs to generate germinal center B cells, plasma cells

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