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  • Turning Discoveries into Treatments: Immunology in Africa
    Trends Immunol. (IF 13.422) Pub Date : 2020-11-04
    Faith H.A. Osier; Henry C. Mwandumba; Clive M. Gray

    An exemplar outcome of an immunology-based intervention is vaccine development; the current COVID-19 pandemic is a case in point. Can we build an immunology research ecosystem in Africa that nurtures discovery and enables translation? We see African immunologists as key agents of change and discuss obstacles and opportunities.

  • Lysozyme: A Double-Edged Sword in the Intestine
    Trends Immunol. (IF 13.422) Pub Date : 2020-11-03
    Mor Zigdon; Shai Bel

    Lysozyme-secreting Paneth cells are abnormally present in the distal colons of patients with inflammatory bowel disease (IBD), along with high amounts of lysozyme in feces. In a recent article in Immunity, Yu et al. show that lysozyme-mediated processing of luminal bacteria in the colon triggers a proinflammatory response and predisposes mice to experimental IBD.

  • Endogenous Labeling for Light Microscopy during HIV-1 Immune Responses
    Trends Immunol. (IF 13.422) Pub Date : 2020-11-02
    Minette Salmon; Irene Carlon-Andres; Sergi Padilla-Parra

    New approaches in single molecule spectroscopy and microscopy are able to resolve the spatial and temporal resolution of T cell receptor signaling in the context of immune responses to HIV-1 infection. These approaches need to be complemented with novel techniques that endogenously tag the protein or proteins of interest, yet avoid overexpression, to image protein dynamics under physiological conditions

  • On the Improper Use of the Term High-Density Neutrophils
    Trends Immunol. (IF 13.422) Pub Date : 2020-11-04
    Marco A. Cassatella; Patrizia Scapini

    Recent studies have revealed that neutrophils exhibit an unsuspected heterogeneity. In this context, the term high-density neutrophils (HDNs) has recently gained ground to define nothing more than neutrophils displaying an unaltered normal density. Therefore, as discussed here, we argue that the HDNs term must be avoided, as it is confounding and scientifically inappropriate.

  • Decoding the Heterogeneity of Human Dendritic Cell Subsets
    Trends Immunol. (IF 13.422) Pub Date : 2020-10-23
    Javiera Villar; Elodie Segura

    Dendritic cells (DCs) have been classified into distinct subsets based on phenotype and ontogeny. In the past few years, high throughput single-cell approaches have revealed further heterogeneity of human DCs, in particular at the transcriptomic level. Herein examined, are recent studies describing new human DC populations based on single-cell RNA-seq analysis, and a unified view of these emerging

  • Noradrenergic Signaling and Neuroinflammation Crosstalk Regulate Toxoplasma gondii-Induced Behavioral Changes
    Trends Immunol. (IF 13.422) Pub Date : 2020-11-16
    Conor Laing; Nicolas Blanchard; Glenn A. McConkey

    Infections of the nervous system elicit neuroimmune responses and alter neurotransmission, affecting host neurological functions. Chronic infection with the apicomplexan parasite Toxoplasma correlates with certain neurological disorders in humans and alters behavior in rodents. Here, we propose that the crosstalk between neurotransmission and neuroinflammation may underlie some of these cognitive changes

  • Coronaviruses: Innate Immunity, Inflammasome Activation, Inflammatory Cell Death, and Cytokines
    Trends Immunol. (IF 13.422) Pub Date : 2020-10-15
    SangJoon Lee; Rudragouda Channappanavar; Thirumala-Devi Kanneganti

    The innate immune system acts as the first line of defense against pathogens, including coronaviruses (CoVs). Severe acute respiratory syndrome (SARS)-CoV and Middle East respiratory syndrome (MERS)-CoV are epidemic zoonotic CoVs that emerged at the beginning of the 21st century. The recently emerged virus SARS-CoV-2 is a novel strain of CoV that has caused the coronavirus 2019 (COVID-19) pandemic

  • Mechanisms of SARS-CoV-2 Transmission and Pathogenesis
    Trends Immunol. (IF 13.422) Pub Date : 2020-10-14
    Andrew G. Harrison; Tao Lin; Penghua Wang

    The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) marks the third highly pathogenic coronavirus to spill over into the human population. SARS-CoV-2 is highly transmissible with a broad tissue tropism that is likely perpetuating the pandemic. However, important questions remain regarding its transmissibility and pathogenesis. In this review, we summarize current SARS-CoV-2

  • Zebrafish Models to Study Inflammasome-Mediated Regulation of Hematopoiesis
    Trends Immunol. (IF 13.422) Pub Date : 2020-11-05
    Lola Rodríguez-Ruiz; Juan M. Lozano-Gil; Christophe Lachaud; Pablo Mesa-del-Castillo; María L. Cayuela; Diana García-Moreno; Ana B. Pérez-Oliva; Victoriano Mulero

    Hematopoiesis is a complex process through which immature bone marrow precursor cells mature into all types of blood cells. Although the association of hematopoietic lineage bias (including anemia and neutrophilia) with chronic inflammatory diseases has long been appreciated, the causes involved are obscure. Recently, cytosolic multiprotein inflammasome complexes were shown to activate inflammatory

  • Regulation of Normal and Malignant Hematopoiesis by FBOX Ubiquitin E3 Ligases
    Trends Immunol. (IF 13.422) Pub Date : 2020-11-04
    R. Willow Hynes-Smith; Karli J. Wittorf; Shannon M. Buckley

    Hematopoiesis is responsible for numerous functions, ranging from oxygen transportation to host defense, to injury repair. This process of hematopoiesis is maintained throughout life by hematopoietic stem cells and requires a controlled balance between self-renewal, differentiation, and quiescence. Disrupting this balance can result in hematopoietic malignancies, including anemia, immune deficiency

  • NF-κB and Extrinsic Cell Death Pathways – Entwined Do-or-Die Decisions for T cells
    Trends Immunol. (IF 13.422) Pub Date : 2020-11-24
    Sam Blanchett; Ines Boal-Carvalho; Scott Layzell; Benedict Seddon

    NF-κB signaling is required at multiple stages of T cell development and function. The NF-κB pathway integrates signals from many receptors and involves diverse adapters and kinases. Recent advances demonstrate that kinases controlling NF-κB activation, such as the IKK complex, serve dual independent functions because they also control cell death checkpoints. Survival functions previously attributed

  • T Cells: Warriors of SARS-CoV-2 Infection
    Trends Immunol. (IF 13.422) Pub Date : 2020-11-13
    Paola de Candia; Francesco Prattichizzo; Silvia Garavelli; Giuseppe Matarese

    Severe infection with SARS-CoV-2 is characterized by massive cytokine release and T cell loss. The exaggerated host immune response, incapable of viral clearance, instead aggravates respiratory distress, as well as cardiac and/or damage to other organs. The mortality pattern of SARS-CoV-2 infection, higher in older vs younger adults and almost absent in children, is possibly caused by the effects of

  • Combining Antivirals and Immunomodulators to Fight COVID-19
    Trends Immunol. (IF 13.422) Pub Date : 2020-11-13
    Vincent Feuillet; Bruno Canard; Alain Trautmann

    The majority of SARS-CoV-2-infected individuals remain paucisymptomatic, contrasting with a minority of infected individuals in danger of death. Here, we speculate that the robust disease resistance of most individuals is due to a swift production of type I interferon (IFNα/β), presumably sufficient to lower the viremia. A minority of infected individuals with a preexisting chronic inflammatory state

  • A Potential Role of Interleukin-10 in COVID-19 Pathogenesis
    Trends Immunol. (IF 13.422) Pub Date : 2020-11-02
    Ligong Lu; Hui Zhang; Danielle J. Dauphars; You-Wen He

    A unique feature of the cytokine storm in COVID-19 is the dramatic elevation of IL-10. Its significance was thought as a negative-feedback mechanism for suppressing inflammation. However, several lines of clinical evidence suggest that dramatic early pro-inflammatory IL-10 elevation might play a pathological role in COVID-19 severity.

  • The Complement C5a-C5aR1 GPCR Axis in COVID-19 Therapeutics
    Trends Immunol. (IF 13.422) Pub Date : 2020-09-23
    Trent M. Woodruff; Arun K. Shukla

    The current pandemic of coronavirus disease (COVID-19) caused by SARS-CoV-2 is a significant global health challenge. A recent study by Carvelli and colleagues now demonstrates the involvement of complement C5a and its receptor C5aR1 in disease progression and suggests that blockade of the C5a-C5aR1 axis may represent a potential therapeutic strategy against COVID-19.

  • Can Microbes Boost Tregs to Suppress Food Sensitivities?
    Trends Immunol. (IF 13.422) Pub Date : 2020-10-06
    Magdalena Siller; Yanlin Zeng; Reinhard Hinterleitner

    Food sensitivities are on the rise worldwide. Peripheral induced regulatory T cells (pTreg cells) play a central role in oral tolerance to dietary antigens and can contribute to preventing the onset of immune-mediated food sensitivities. Here, we discuss the potential of microbial-derived products in promoting pTreg cell proliferation for re-establishing oral tolerance in immune-mediated food sensitivities

  • The Role of CD8 Downregulation during Thymocyte Differentiation
    Trends Immunol. (IF 13.422) Pub Date : 2020-10-07
    Aneela Nomura; Ichiro Taniuchi

    During mammalian T cell development, CD4+CD8+ double-positive (DP) thymocytes must make a lineage choice to become either conventional CD4+ or CD8+ T cells, dependent on their specificity for MHC-II or MHC-I, respectively. Alternatively, DP thymocytes can decide to become innate-like T cells in response to nonclassical MHC-I molecules. A key feature is the downregulation of CD8, which causes transient

  • The Paradoxical Roles of Inflammation during PD-1 Blockade in Cancer
    Trends Immunol. (IF 13.422) Pub Date : 2020-10-06
    Marcelo Hill; Mercedes Segovia; Sofía Russo; Maria Romina Girotti; Gabriel A. Rabinovich

    Recent studies have reported paradoxical roles of inflammation in tumor immunity triggered by PD-1 checkpoint antibody (Ab) blockade. Here, we elaborate on this controversy and propose a new perspective that might help understand this paradox. Since inflammatory cytokines and PD-1 blockade are known to target different subsets of exhausted CD8+ T cells, we propose that the timing at which anti-PD-1

  • Illuminating Epigenetics and Inheritance in the Immune System with Bioluminescence
    Trends Immunol. (IF 13.422) Pub Date : 2020-10-06
    Andrew Dimond; Mathew Van de Pette; Amanda G. Fisher

    The remarkable process of light emission by living organisms has fascinated mankind for thousands of years. A recent expansion in the repertoire of catalytic luciferase enzymes, coupled with the discovery of the genes and pathways that encode different luciferin substrates, means that bioluminescence imaging (BLI) is set to revolutionize longitudinal and dynamic studies of gene control within biomedicine

  • Structural Basis of SARS-CoV-2 and SARS-CoV Antibody Interactions
    Trends Immunol. (IF 13.422) Pub Date : 2020-09-17
    Edem Gavor; Yeu Khai Choong; Shi Yin Er; Hariharan Sivaraman; J. Sivaraman

    The 2019 coronavirus pandemic remains a major public health concern. Neutralizing antibodies (nAbs) represent a cutting-edge antiviral strategy. We focus here on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and SARS-CoV, and discuss current progress in antibody research against rampant SARS-CoV-2 infections. We provide a perspective on the mechanisms of SARS-CoV-2-derived nAbs, comparing

  • Transcription Factor Bhlhe40 in Immunity and Autoimmunity
    Trends Immunol. (IF 13.422) Pub Date : 2020-10-07
    Melissa E. Cook; Nicholas N. Jarjour; Chih-Chung Lin; Brian T. Edelson

    The basic helix-loop-helix transcription factor (TF) Bhlhe40 is emerging as a key regulator of immunity during infection, autoimmunity, and inflammatory conditions. We describe the roles of Bhlhe40 in the circulating and tissue-resident arms of the immune system, with emphasis on recent work on the regulation of cytokine production and proliferation. We explore the mechanisms behind these functions

  • Polyamines and Kynurenines at the Intersection of Immune Modulation
    Trends Immunol. (IF 13.422) Pub Date : 2020-10-12
    Elisa Proietti; Sofia Rossini; Ursula Grohmann; Giada Mondanelli

    Polyamines (i.e., putrescine, spermidine, and spermine) are bioactive polycations capable of binding nucleic acids and proteins and modulating signaling pathways. Polyamine functions have been studied most extensively in tumors, where they can promote cell transformation and proliferation. Recently, spermidine was found to exert protective effects in an experimental model of multiple sclerosis (MS)

  • Modeling Potential Autophagy Pathways in COVID-19 and Sarcoidosis.
    Trends Immunol. (IF 13.422) Pub Date : 2020-08-10
    Alain Calender,Dominique Israel-Biet,Dominique Valeyre,Yves Pacheco

    Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and mainly affects the lungs. Sarcoidosis is an autoinflammatory disease characterized by the diffusion of granulomas in the lungs and other organs. Here, we discuss how the two diseases might involve some common mechanistic cellular pathways around the regulation of autophagy.

  • Cell Cycle Regulation Meets Tumor Immunosuppression.
    Trends Immunol. (IF 13.422) Pub Date : 2020-08-13
    Jinyang Li,Ben Z Stanger

    Reciprocal interactions between tumor cells and immune cells shape the tumor microenvironment. Recent studies indicate that enhanced cell cycle activity in cancer cells suppresses antitumor immunity. Herein we discuss potential mechanisms by which cell cycle programs intrinsic to tumor cells are coupled to immune behavior, with consequences for immunotherapy.

  • Teaching Old Dogs New Tricks? The Plasticity of Lung Alveolar Macrophage Subsets.
    Trends Immunol. (IF 13.422) Pub Date : 2020-09-04
    Justina Kulikauskaite,Andreas Wack

    Alveolar macrophages (AMs) are highly abundant lung cells with important roles in homeostasis and immunity. Their function influences the outcome of lung infections, lung cancer, and chronic inflammatory disease. Recent findings reveal functional heterogeneity of AMs. Following lung insult, resident AMs can either remain unchanged, acquire new functionality, or be replaced by monocyte-derived AMs.

  • CRAC Channels and Calcium Signaling in T Cell-Mediated Immunity.
    Trends Immunol. (IF 13.422) Pub Date : 2020-07-22
    Martin Vaeth,Sascha Kahlfuss,Stefan Feske

    Calcium (Ca2+) signals play fundamental roles in immune cell function. The main sources of Ca2+ influx in mammalian lymphocytes following antigen receptor stimulation are Ca2+ release-activated Ca2+ (CRAC) channels. These are formed by ORAI proteins in the plasma membrane and are activated by stromal interaction molecules (STIM) located in the endoplasmic reticulum (ER). Human loss-of-function (LOF)

  • Tissue-Specific Features of Innate Lymphoid Cells.
    Trends Immunol. (IF 13.422) Pub Date : 2020-09-08
    Isabel Meininger,Anna Carrasco,Anna Rao,Tea Soini,Efthymia Kokkinou,Jenny Mjösberg

    Although the function of the circulating immune cell compartment has been studied in detail for decades, limitations in terms of access and cell yields from peripheral tissues have restricted our understanding of tissue-based immunity, particularly in humans. Recent advances in high-throughput protein analyses, transcriptional profiling, and epigenetics have partially overcome these obstacles. Innate

  • Protein Arginine Methyltransferase 5 in T Lymphocyte Biology.
    Trends Immunol. (IF 13.422) Pub Date : 2020-09-02
    Shouvonik Sengupta,Austin Kennemer,Kristin Patrick,Philip Tsichlis,Mireia Guerau-de-Arellano

    Protein arginine methyltransferase 5 (PRMT5) is the major methyltransferase (MT) catalyzing symmetric dimethylation (SDM). PRMT5 regulates developmental, homeostatic and disease processes in vertebrates and invertebrates, and a carcinogenic role has been observed in mammals. Recently, tools generated for PRMT5 loss of function have allowed researchers to demonstrate essential roles for PRMT5 in mouse

  • miRNA-Based Therapies in B Cell Non-Hodgkin Lymphoma.
    Trends Immunol. (IF 13.422) Pub Date : 2020-09-01
    Teresa Fuertes,Almudena R Ramiro,Virginia G de Yebenes

    Non-Hodgkin lymphoma (NHL) is a diverse class of hematological cancers, many of which arise from germinal center (GC)-experienced B cells. Thus GCs, the sites of antibody affinity maturation triggered during immune responses, also provide an environment that facilitates B cell oncogenic transformation. miRNAs provide attractive and mechanistically different strategies to treat these malignancies based

  • Overcoming Immune Checkpoint Blockade Resistance via EZH2 Inhibition
    Trends Immunol. (IF 13.422) Pub Date : 2020-09-24
    Hye-Jung Kim; Harvey Cantor; Kat Cosmopoulos

    Recent progress in cancer immunotherapy highlights the power of the immune system to control tumors, although a small patient subset responds to current immunotherapies. Additional approaches to mobilize antitumor immunity are required to overcome primary and acquired resistance to immunotherapy such as immune checkpoint blockade (ICB). Emerging evidence shows that targeting epigenetic elements that

  • 更新日期:2020-09-01
  • Microglia and Astrocyte Crosstalk in Immunity.
    Trends Immunol. (IF 13.422) Pub Date : 2020-09-01
    Catarina Sacristán

  • The Burden of Memory: Response to Ortega.
    Trends Immunol. (IF 13.422) Pub Date : 2020-08-28
    Ger Rijkers

  • Location, Location, Location: Transcriptional Control of Astrocyte Heterogeneity.
    Trends Immunol. (IF 13.422) Pub Date : 2020-08-12
    Marci F Rosenberg,Anna V Molofsky

    Huang et al. have found that deletion of astrocyte lineage-specifying transcription factor NFIA from mature astrocytes alters astrocyte morphology, molecular identity, and synaptic-support capacity in a region-specific manner. We discuss the implications of these findings in light of emerging roles for astrocytes in immune cell crosstalk.

  • A Gut Feeling about C9ORF72.
    Trends Immunol. (IF 13.422) Pub Date : 2020-08-13
    Magdalini Polymenidou

    C9ORF72 mutations are the most common genetic cause of ALS and FTD, leading to neurodegeneration via complex mechanisms. Mutations also lead to loss of C9ORF72 function and inflammatory diseases in patients and knockout mice. Burberry et al. now show that C9orf72-associated inflammation and premature death in mice are directly modified by the gut microbiome.

  • Astrocyte Reactivity: Subtypes, States, and Functions in CNS Innate Immunity.
    Trends Immunol. (IF 13.422) Pub Date : 2020-08-17
    Michael V Sofroniew

    Astrocytes are neural parenchymal cells that ubiquitously tile the central nervous system (CNS). In addition to playing essential roles in healthy tissue, astrocytes exhibit an evolutionarily ancient response to all CNS insults, referred to as astrocyte reactivity. Long regarded as passive and homogeneous, astrocyte reactivity is being revealed as a heterogeneous and functionally powerful component

  • To Kill a Microglia: A Case for CSF1R Inhibitors.
    Trends Immunol. (IF 13.422) Pub Date : 2020-08-10
    Kim N Green,Joshua D Crapser,Lindsay A Hohsfield

    Microglia, the brain’s immune sentinels, have garnered much attention in recent years. Researchers have begun to identify the manifold roles that these cells play in the central nervous system (CNS), and this work has been greatly facilitated by microglial depletion paradigms. The varying degrees of spatiotemporal manipulation afforded by such techniques allow microglial ablation before, during, and/or

  • Investigating Microglia in Health and Disease: Challenges and Opportunities.
    Trends Immunol. (IF 13.422) Pub Date : 2020-07-28
    Veronique E Miron,Josef Priller

    Microglia are tissue-resident macrophages implicated in central nervous system (CNS) development, homeostasis, and response to injury. Recent advances in transcriptomics, multiplex protein expression analysis, and experimental depletion of microglia have cemented their importance. However, it is still unclear which models are best suited to investigate microglia and explore their function in human

  • Immunological Features of Non-neuronal Brain Cells: Implications for Alzheimer's Disease Immunotherapy.
    Trends Immunol. (IF 13.422) Pub Date : 2020-08-13
    Giulia Castellani,Michal Schwartz

    An interaction network exists among cells within the brain, maintaining brain homeostasis and ensuring its functional plasticity. In addition to neurons, participating cells include astrocytes, oligodendrocytes, and microglia. Peripheral immune cells, such as monocytes and lymphocytes, have also been found to play an important role in supporting the brain in health and assisting in its repair. Here

  • The Role of Astrocytes in CNS Inflammation.
    Trends Immunol. (IF 13.422) Pub Date : 2020-08-13
    Federico Giovannoni,Francisco J Quintana

    Astrocytes are the most abundant cell type in the central nervous system (CNS), performing complex functions in health and disease. It is now clear that multiple astrocyte subsets or activation states (plastic phenotypes driven by intrinsic and extrinsic cues) can be identified, associated to specific genomic programs and functions. The characterization of these subsets and the mechanisms that control

  • Microglia and Astrocytes in Disease: Dynamic Duo or Partners in Crime?
    Trends Immunol. (IF 13.422) Pub Date : 2020-08-17
    Shane A Liddelow,Samuel E Marsh,Beth Stevens

    Microglia–astrocyte interactions represent a delicate balance affecting neural cell functions in health and disease. Tightly controlled to maintain homeostasis during physiological conditions, rapid and prolonged departures during disease, infection, and following trauma drive multiple outcomes: both beneficial and detrimental. Recent sequencing studies at the bulk and single-cell level in humans and

  • The Role of TGFβ Signaling in Microglia Maturation and Activation.
    Trends Immunol. (IF 13.422) Pub Date : 2020-07-30
    Björn Spittau,Nikolaos Dokalis,Marco Prinz

    The pleiotropic cytokine transforming growth factor-beta 1 (TGFβ1) plays pivotal roles in different cell types, including immune cells such as T cells, monocytes/macrophages, and microglia. Microglia are essential during physiological and pathological events. Maturation of postnatal microglia, as well as the regulation of the complex functional repertoire of microglia, needs to be carefully orchestrated

  • Is Immunological Memory a Burden in Times of COVID-19?
    Trends Immunol. (IF 13.422) Pub Date : 2020-08-12
    Enrique Ortega

  • 更新日期:2020-08-11
  • Does Cross-neutralization of SARS-CoV-2 Only Relate to High Pathogenic Coronaviruses?
    Trends Immunol. (IF 13.422) Pub Date : 2020-08-08
    Zhongren Ma,Pengfei Li,Aqsa Ikram,Qiuwei Pan

  • 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.

  • Redefining Memory T Cell Subsets.
    Trends Immunol. (IF 13.422) Pub Date : 2020-07-06
    Rod A Rahimi,Andrew D Luster

    It has become increasingly clear that the terms used to define memory T cell subsets no longer accurately reflect our understanding of memory T cell biology. Here, we discuss the limitations of our current terminology and propose a new approach for defining memory T cell subsets.

  • 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

  • Organoid Models of Tumor Immunology.
    Trends Immunol. (IF 13.422) Pub Date : 2020-07-09
    Kanako Yuki,Ning Cheng,Michitaka Nakano,Calvin J Kuo

    Cellular interactions in the tumor microenvironment (TME) significantly govern cancer progression and drug response. The efficacy of clinical immunotherapies has fostered an exponential interest in the tumor immune microenvironment, which in turn has engendered a pressing need for robust experimental systems modeling patient-specific tumor–immune interactions. Traditional 2D in vitro tumor immunotherapy

  • 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

  • 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

  • Understanding Normal and Malignant Human Hematopoiesis Using Next-Generation Humanized Mice.
    Trends Immunol. (IF 13.422) Pub Date : 2020-07-03
    Yoriko Saito,Leonard D Shultz,Fumihiko Ishikawa

    Rodent models for human diseases contribute significantly to understanding human physiology and pathophysiology. However, given the accelerating pace of drug development, there is a crucial need for in vivo preclinical models of human biology and pathology. The humanized mouse is one tool to bridge the gap between traditional animal models and the clinic. The development of immunodeficient mouse strains

  • Activation and Suppression of Group 3 Innate Lymphoid Cells in the Gut.
    Trends Immunol. (IF 13.422) Pub Date : 2020-07-06
    Wenqing Zhou,Gregory F Sonnenberg

    Group 3 innate lymphoid cells (ILC3s) have emerged as master regulators of intestinal health and tissue homeostasis in mammals. Through a diverse array of cytokines and cellular interactions, ILC3s crucially orchestrate lymphoid organogenesis, promote tissue protection or regeneration, facilitate antimicrobial responses, and directly regulate adaptive immunity. Further, translational studies have found

  • 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

  • Using Serology with Models to Clarify the Trajectory of the SARS-CoV-2 Emerging Outbreak.
    Trends Immunol. (IF 13.422) Pub Date : 2020-06-29
    C Jessica E Metcalf,Cecile Viboud,David J Spiro,Bryan T Grenfell

  • 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

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