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  • Nuclear Receptors in Cancer Inflammation and Immunity
    Trends Immunol. (IF 13.000) 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, and the biological features of immune cells that express specific NRs in the context of cancer. NR-dependent alterations in tumor inflammation and immunity may be amenable to pharmacological manipulation and offer new clues regarding the development of novel cancer therapeutic regimens.

    更新日期:2020-01-22
  • Metabolic Adaptations to Infections at the Organismal Level
    Trends Immunol. (IF 13.000) 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 approaches to treat disease. Here, we review topical findings in organismal metabolism and infection and highlight four emerging lines of investigation: how host–microbiota metabolic partnerships protect against infection; competition for glucose between host and pathogen; significance of infection-induced anorexia; and redefinition of the role of iron during infection. We also discuss how these discoveries shape our understanding of infection biology and their likely therapeutic value.

    更新日期:2020-01-21
  • Key Roles of MiT Transcription Factors in Innate Immunity and Inflammation
    Trends Immunol. (IF 13.000) 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 of phagocytosis, interferon (IFN)-γ, lipopolysaccharide (LPS), and adenosine receptors. Moreover, overexpression of TFEB or TFE3 can drive inflammation in vivo, such as in atherosclerosis, while in other scenarios they can perform anti-inflammatory functions. MiT factors may constitute potential therapeutic targets for a broad range of diseases; however, to harness their therapeutic potential, sophisticated ways to manipulate MiT factor activity safely and effectively must be developed.

    更新日期:2020-01-17
  • Skin-Resident Innate Lymphoid Cells – Cutaneous Innate Guardians and Regulators
    Trends Immunol. (IF 13.000) 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 innate lymphoid cells (ILCs). Here, we discuss advances demonstrating how skin ILCs contribute to tissue homeostasis by regulating microbiome balance in steady-state and how their dysregulation can trigger and promote inflammatory skin diseases such as atopic dermatitis and psoriasis. We review the phenotypic and functional similarities and differences of ILCs between the skin and other organs and highlight future areas of investigation for this field.

    更新日期:2020-01-14
  • ACLY-matizing Macrophages to Histone Modification during Immunometabolic Reprogramming
    Trends Immunol. (IF 13.000) 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.

    更新日期:2020-01-13
  • Mitochondrial and Purinergic Dysregulation Promote Abnormal Behavior in Mice
    Trends Immunol. (IF 13.000) 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.

    更新日期:2020-01-13
  • Control of Stimulus-Dependent Responses in Macrophages by SWI/SNF Chromatin Remodeling Complexes
    Trends Immunol. (IF 13.000) 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 of the SWI/SNF complex was identified with unknown function in inflammatory gene regulation. Here, we summarize the biochemical and genomic properties of SWI/SNF complex variants and the potential for increased regulatory control of innate immune transcriptional programs in light of such biochemical diversity. Finally, we review the development of SWI/SNF complex chemical inhibitors and degraders that could be used to modulate immune responses.

    更新日期:2020-01-09
  • Human Secretory IgM: An Elusive Player in Mucosal Immunity
    Trends Immunol. (IF 13.000) 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 examination of SIgMs and their corresponding B cell secretors in several different pathological immunological contexts, we review the presumed role of these molecules in gut tolerance, inflammatory bowel diseases, and lung immunity. As SIgMs harbor a mostly tolerogenic function, we posit that their inclusion in further immunological research is paramount.

    更新日期:2020-01-09
  • Stressed-Out T Cells Fragment the Mind
    Trends Immunol. (IF 13.000) 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.

    更新日期:2020-01-06
  • From Loops to Looks: Transcription Factors and Chromatin Organization Shaping Terminal B Cell Differentiation
    Trends Immunol. (IF 13.000) 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 and memory B cells. Recent evidence indicates that mature B cell formation involves an essential contribution from 3D chromatin conformations through its interplay with transcription factors and epigenetic machinery. Here, we provide an up-to-date overview of the coordination between transcription factors, epigenetic changes, and chromatin architecture during terminal B cell differentiation, focusing on recent discoveries and technical advances for studying 3D chromatin structures.

    更新日期:2019-12-07
  • T Cell Antifungal Immunity and the Role of C-Type Lectin Receptors
    Trends Immunol. (IF 13.000) Pub Date : 2019-12-05
    Emily A. Speakman, Ivy M. Dambuza, Fabián Salazar, Gordon D. Brown

    Fungi can cause disease in humans, from mucocutaneous to life-threatening systemic infections. Initiation of antifungal immunity involves fungal recognition by pattern recognition receptors such as C-type lectin receptors (CLRs). These germline-encoded receptors trigger a multitude of innate responses including phagocytosis, fungal killing, and antigen presentation which can also shape the development of adaptive immunity. Recently, studies have shed light on how CLRs directly or indirectly modulate lymphocyte function. Moreover, CLR-mediated recognition of commensal fungi maintains homeostasis and prevents invasion from opportunistic commensals. We present an overview of current knowledge of antifungal T cell immune responses, with emphasis on the role of C-type lectins, and discuss how these receptors modulate these responses at different levels.

    更新日期:2019-12-06
  • Detrimental Role of Neutrophil Extracellular Traps during Dengue Virus Infection
    Trends Immunol. (IF 13.000) Pub Date : 2019-12-05
    Claudia Schulz, Gülsah Gabriel, Maren von Köckritz-Blickwede

    A recent article by Sung et al. identified the CLEC2 platelet receptor as an important factor of lethal dengue virus infection. Formation of neutrophil extracellular traps via crosstalk with CLEC5A and TLR2 neutrophils were ascribed a causative role in DENV infection. This provides new insights for the development of candidate broad-spectrum therapies against hemorrhagic virus infections.

    更新日期:2019-12-06
  • Epigenetic Regulation of T Cell Memory: Recalling Therapeutic Implications
    Trends Immunol. (IF 13.000) Pub Date : 2019-12-05
    David F. Tough, Inma Rioja, Louise K. Modis, Rab K. Prinjha

    Memory T cells possess functional differences from naïve T cells that powerfully contribute to the efficiency of secondary immune responses. These abilities are imprinted during the primary response, linked to the acquisition of novel patterns of gene expression. Underlying this are alterations at the chromatin level (epigenetic modifications) that regulate constitutive and inducible gene transcription. T cell epigenetic memory can persist long-term, contributing to long-lasting immunity after infection or vaccination. However, acquired epigenetic states can also hinder effective tumor immunity or contribute to autoimmunity. The growing understanding of epigenetic gene regulation as it relates to both the stability and malleability of T cell memory may offer the potential to selectively modify T cell memory in disease by targeting epigenetic mechanisms.

    更新日期:2019-12-05
  • Stem, Effector, and Hybrid States of Memory CD8+ T Cells
    Trends Immunol. (IF 13.000) Pub Date : 2019-12-04
    Enrico Lugli, Giovanni Galletti, Shannon K. Boi, Benjamin A. Youngblood

    CD8+ T cell immunological memory of past antigen exposure can confer long-lived protection against infections or tumors. The fact that CD8+ memory T cells can have features of both naïve and effector cells has forced the field to struggle with several conceptual questions about the developmental origin of the cell and, consequently, the mechanism(s) that contribute to memory development. Here, we discuss recent conceptual advances in our understanding of memory T cell development that incorporate data describing a hybrid stem and/or effector state of differentiation. We theorize that the mechanisms involved in developing these cells could be mediated, in part, through epigenetic programs. Finally, we consider the potential therapeutic implications of inducing and/or utilizing such hybrid cells clinically.

    更新日期:2019-12-04
  • Genetic Variation Shapes Murine Gut Microbiota via Immunity
    Trends Immunol. (IF 13.000) Pub Date : 2019-12-03
    Emily R. Davenport

    Host genetics influence gut microbiome composition. However, determining the specific physiological mechanisms and microbes affected has been difficult due to ‘cage’ and ‘legacy’ effects in model systems. Recently, Khan et al. cleverly colonized ex-germ-free mice to demonstrate that immune genes regulate select bacterial lineages in the mouse gut.

    更新日期:2019-12-04
  • Distinct Regulatory and Effector T Cell Metabolic Demands during Graft-Versus-Host Disease
    Trends Immunol. (IF 13.000) Pub Date : 2019-11-30
    Keli L. Hippen, Ethan G. Aguilar, Stephanie Y. Rhee, Sara Bolivar-Wagers, Bruce R. Blazar

    Despite graft-versus-host disease (GVHD) prophylactic agents, the success and wider utilization of allogeneic hematopoietic stem cell transplantation (allo-HSCT) is limited by GVHD. Increasing donor graft regulatory T cell (Treg):effector T cell (Teff) ratios can substantially reduce GVHD in cancer patients, but pre-HSCT conditioning regimens and GVHD create a challenging inflammatory environment for Treg stability, persistence, and function. Metabolism plays a crucial role in T cell and Treg differentiation, and development of effector function. Although glycolysis is a main driver of allogeneic T cell-driven GVHD, oxidative phosphorylation is a main driver of Treg suppressor function. This review focuses on recent advances in our understanding of Treg metabolism in the context of GVHD, and discusses potential therapeutic applications of Tregs in the prevention or treatment of GVHD in cancer patients.

    更新日期:2019-11-30
  • ILC2s in High Definition: Decoding the Logic of Tissue-Based Immunity
    Trends Immunol. (IF 13.000) Pub Date : 2019-11-29
    Do-Hyun Kim, Steven J. Van Dyken

    Group 2 innate lymphoid cells (ILC2s) mediate allergic immunity but have also recently come into focus as key sentinels of tissue health and homeostasis. Clues as to how these rare immune cells coordinate tissue-wide responses to perturbation have emerged from deciphering the communication between ILC2s and an ever-expanding list of diverse nonhematopoietic cells. High-resolution tracking and profiling approaches have accelerated these efforts, revealing ILC2 transcriptional programs that are coordinated with tissue and organism development. We propose that the engagement of these homeostatic feedback circuits by internal and external cues forms the basis for how tissues instruct type 2 immunity. Understanding how these normally restorative networks become unbalanced may be crucial in devising appropriately targeted therapies for allergic diseases.

    更新日期:2019-11-30
  • Impact of Historic Migrations and Evolutionary Processes on Human Immunity
    Trends Immunol. (IF 13.000) Pub Date : 2019-11-27
    Jorge Domínguez-Andrés, Mihai G. Netea

    The evolution of mankind has constantly been influenced by the pathogens encountered. The various populations of modern humans that ventured out of Africa adapted to different environments and faced a large variety of infectious agents, resulting in local adaptations of the immune system for these populations. The functional variation of immune genes as a result of evolution is relevant in the responses against infection, as well as in the emergence of autoimmune and inflammatory diseases observed in modern populations. Understanding how host–pathogen interactions have influenced the human immune system from an evolutionary perspective might contribute to unveiling the causes behind different immune-mediated disorders and promote the development of new strategies to detect and control such diseases.

    更新日期:2019-11-28
  • Emerging Role of Mitochondrial DNA as a Major Driver of Inflammation and Disease Progression
    Trends Immunol. (IF 13.000) Pub Date : 2019-11-16
    Fei Zhong, Shuang Liang, Zhenyu Zhong

    Inflammation benefits the host by promoting the elimination of invading pathogens and clearance of cellular debris after tissue injury. Inflammation also stimulates tissue repair and regeneration to restore homeostasis and organismal health. Emerging evidence suggests that mitochondrial DNA (mtDNA), the only form of non-nuclear DNA in eukaryotic cells, is a major activator of inflammation when leaked out from stressed mitochondria. Here, we review the current understanding on the role of mtDNA in innate immunity, discussing how dysregulated mtDNA metabolism can promote chronic inflammation and disease progression.

    更新日期:2019-11-17
  • Stimulation of Innate Immunity by Host and Viral RNAs
    Trends Immunol. (IF 13.000) Pub Date : 2019-11-14
    Felix Streicher, Nolwenn Jouvenet

    The interferon (IFN) response, a major vertebrate defense mechanism against viral infections, is initiated by RIG-I-like receptor (RLR)-mediated recognition of viral replicative intermediates in the cytosol. RLR purification methods coupled to RNA sequencing have recently led to the characterization of viral nucleic acid features recognized by RLRs in infected cells. This work revealed that some cellular RNAs can bind to RLRs and stimulate the IFN response. We provide an overview of self and non-self RNAs that activate innate immunity, and discuss the cellular dysregulation that allows recognition of cellular RNAs by RLRs, including RNA mislocalization and downregulation of RNA-shielding proteins. These discussions are relevant because manipulating RLR activation presents opportunities for treating viral infections and autoimmune disorders.

    更新日期:2019-11-14
  • Targeting Apoptosis Inhibition to Activate Antitumor Immunity
    Trends Immunol. (IF 13.000) Pub Date : 2019-11-14
    Sannula Kesavardhana, Thirumala-Devi Kanneganti

    A recent study by Rodriguez-Ruiz et al. suggests that inhibition of apoptotic caspases can augment radiation-induced antitumor immunity, independent of type I IFN. Their findings also highlight caspase-independent cytotoxicity in radiation therapy-induced antitumor immunity, proposing SLC7A2 as a new putative prognostic marker for breast cancer.

    更新日期:2019-11-14
  • Kupffer Cells Mediate Systemic Antifungal Immunity
    Trends Immunol. (IF 13.000) Pub Date : 2019-11-14
    Carolina Coelho, Rebecca A. Drummond

    Patients with liver dysfunction have increased susceptibility to fungal infections. A recently published article (Sun et al.) describes the potential mechanism underlying this association, which maps to the antifungal activity of liver-resident Kupffer cells. This research highlights the importance of understanding tissue-specific immune responses in disease pathogenesis.

    更新日期:2019-11-14
  • Control of Lymphocyte Fate, Infection, and Tumor Immunity by TCF-1
    Trends Immunol. (IF 13.000) Pub Date : 2019-11-14
    Dinesh Raghu, Hai-Hui Xue, Lisa A. Mielke

    T cell factor-1 (TCF-1), encoded by Tcf7, is a transcription factor and histone deacetylase (HDAC) essential for commitment to both the T cell and the innate lymphoid cell (ILC) lineages in mammals. In this review, we discuss the multifunctional role of TCF-1 in establishing these lineages and the requirement for TCF-1 throughout lineage differentiation and maintenance of lineage stability. We highlight recent reports showing promise for TCF-1 as a novel biomarker to identify recently characterized subsets of exhausted CD8+ T cells that may help to predict patient responses to immune checkpoint blockade (ICB).

    更新日期:2019-11-14
  • Exhausted-like Group 2 Innate Lymphoid Cells in Chronic Allergic Inflammation
    Trends Immunol. (IF 13.000) Pub Date : 2019-11-14
    Takashi Ebihara, Ichiro Taniuchi

    Mammalian group 2 innate lymphoid cells (ILC2s) are responsible for the early production of type 2 cytokines at mucosal barriers upon exposure to allergen. Inflammatory tissue environmental cues can influence ILC2 activity, and this cellular population can be further categorized into subtypes with additional or alternative functions. Subtypes can include trained (or ‘memory-like’) ILC2s, which recall previous allergic inflammation, inflammatory ILC2s, which acquire the ability to produce IL-17, and ex-ILC2s, which produce ILC1 cytokines. However, the functional states of ILC2s at sites of chronic or severe inflammation are not well characterized. Here, we discuss the emergence of ILC2s with ‘exhausted’-like signatures, and argue that their hyporesponsiveness to stimulation and expression of inhibitory receptors is relevant in mammalian chronic allergic inflammation.

    更新日期:2019-11-14
  • Hidden Aspects of Valency in Immune System Regulation
    Trends Immunol. (IF 13.000) Pub Date : 2019-11-13
    Parimal Samir, Thirumala-Devi Kanneganti

    Valency can be defined as the number of discrete interactions a biomolecule can engage in. Valency can be critical for function, such as determining whether a molecule acts as a scaffold for assembling large supramolecular complexes or forms a functional dimer. Here, we highlight the importance of the role of valency in regulating immune responses, with a focus on innate immunity. We discuss some of the ways in which valency itself is regulated through transcriptional, post-transcriptional, and post-translational modifications. Finally, we propose that the valency model can be applied at the whole cell level to study differences in individual cell responses with relevance to putative therapeutic applications.

    更新日期:2019-11-13
  • Foam Cells: One Size Doesn’t Fit All
    Trends Immunol. (IF 13.000) Pub Date : 2019-11-12
    Valentina Guerrini, Maria Laura Gennaro

    Chronic inflammation in many infectious and metabolic diseases, and some cancers, is accompanied by the presence of foam cells. These cells form when the intracellular lipid content of macrophages exceeds their capacity to maintain lipid homeostasis. Concurrently, critical macrophage immune functions are diminished. Current paradigms of foam cell formation derive from studies of atherosclerosis. However, recent studies indicate that the mechanisms of foam cell biogenesis during tuberculosis differ from those operating during atherogenesis. Here, we review how foam cell formation and function vary with disease context. Since foam cells are therapeutic targets in atherosclerosis, further research on the disease-specific mechanisms of foam cell biogenesis and function is needed to explore the therapeutic consequences of targeting these cells in other diseases.

    更新日期:2019-11-13
  • Inhibition-Resistant CARs for NK Cell Cancer Immunotherapy
    Trends Immunol. (IF 13.000) Pub Date : 2019-11-12
    Xiaoxuan Zhuang, Eric O. Long

    The promise of natural killer (NK) cells as effectors in cancer cellular therapy is limited by their expression of dominant inhibitory receptors for human leukocyte antigen (HLA) class I. Here, we discuss how chimeric antigen receptors (CARs) engineered to override inhibitory signaling might boost NK cell antitumor responses, independently of blockade of NK cell inhibitory receptors.

    更新日期:2019-11-13
  • TCR Ligand Discovery via T-Scan
    Trends Immunol. (IF 13.000) Pub Date : 2019-11-05
    Zhe Wang, Genhong Cheng, Guideng Li

    T cell receptor (TCR) ligand discovery is crucial to monitoring T cell responses to antigen and to identifying antigens reactive against orphan TCRs of interest. In a recent article, Elledge and colleagues describe a functional T cell ligand screening platform for unbiased TCR ligand discovery.

    更新日期:2019-11-05
  • Immune Networks and Therapeutic Targeting of iNKT Cells in Cancer
    Trends Immunol. (IF 13.000) Pub Date : 2019-10-31
    Shin-Ichiro Fujii, Kanako Shimizu

    One of the primary goals in tumor immunotherapy is to reset the immune system from tolerogenic to immunogenic – a process in which invariant natural killer T (iNKT) cells are implicated. iNKT cells develop in the thymus and perform immunosurveillance against tumor cells peripherally. When optimally stimulated, iNKT cells differentiate and display more efficient immune functions. Some cells survive and act as effector memory cells. We discuss the putative roles of iNKT cells in antitumor immunity, and posit that it may be possible to develop novel therapeutic strategies to treat cancers using iNKT cells. In particular, we highlight the challenge of uniquely energizing iNKT cell-licensed dendritic cells to serve as effective immunoadjuvants for both arms of the immune system, thus coupling immunological networks.

    更新日期:2019-11-01
  • piRNA-Guided CRISPR-like Immunity in Eukaryotes
    Trends Immunol. (IF 13.000) Pub Date : 2019-10-31
    Youdiil Ophinni, Umberto Palatini, Yoshitake Hayashi, Nicholas F. Parrish

    Eukaryotic genomes contain virus-derived sequences called endogenous virus elements (EVEs). The majority of EVEs are related to retroviruses, which integrate into the host genome in order to replicate. Some retroviral EVEs encode a function; for example, some produce proteins that block infection by related viruses. EVEs derived from nonretroviral viruses – also recently found in many eukaryotic genomes – are more enigmatic. Here, we summarize the evidence that EVEs can act as templates to generate Piwi-interacting RNAs (piRNAs), whose canonical function is sequence-specific silencing of transposable elements (TEs) to maintain genomic integrity. We argue that EVEs may thus enable heritable, sequence-specific antiviral immune memory in eukaryotes – analogous to CRISPR-Cas immunity in prokaryotes.

    更新日期:2019-11-01
  • A new T-helper cell subset?
    Trends Immunol. (IF 13.000) Pub Date : 2001-03-29
    J Pound

    更新日期:2019-11-01
  • Distinct types of T-cell help for the induction of a humoral immune response to Streptococcus pneumoniae.
    Trends Immunol. (IF 13.000) Pub Date : 2001-05-30
    C M Snapper,Y Shen,A Q Khan,J Colino,P Zelazowski,J J Mond,W C Gause,Z Q Wu

    Studies have indicated that purified soluble polysaccharide antigens can elicit T cell-independent Ig responses in vivo, although these responses can be modulated by T cells in a noncognate manner. Relatively little is known, however, concerning the parameters that regulate polysaccharide-specific, as well as protein-specific, Ig isotype responses to an intact extracellular bacterium. Using the murine in vivo humoral response to intact Streptococcus pneumoniae as a model it can be shown that CD4+ T-cell receptor alphabeta+ T cells deliver help for both polysaccharide- and protein-specific Ig responses. However, these responses differ fundamentally in their mechanism of action.

    更新日期:2019-11-01
  • William E. Paul, MD (1936-2015).
    Trends Immunol. (IF 13.000) Pub Date : 2016-04-12
    Ronald N Germain,B J Fowlkes,Lawrence E Samelson,Warren J Leonard

    更新日期:2019-11-01
  • Apology received.
    Trends Immunol. (IF 13.000) Pub Date : 2005-09-01

    更新日期:2019-11-01
  • Meet the relatives: a family of BPI- and LBP-related proteins.
    Trends Immunol. (IF 13.000) Pub Date : 2004-04-27
    Colin D Bingle,C Jeremy Craven

    Until recently, two key members of the innate immune response to Gram negative bacteria, bactericidal permeability-increasing protein (BPI) and lipopolysaccharide (LPS)-binding protein, have been considered to be members of a small family of lipid-binding proteins that also contains cholesteryl ester transfer protein (CETP) and phospholipid transfer protein (PLTP). A recent paper has characterised three related proteins that are expressed in the mouth, nose and upper airways. Taken together with other recent data, it is clear that a large family of such proteins exists and these additional members might also function in the innate immune response.

    更新日期:2019-11-01
  • 更新日期:2019-11-01
  • New roles for Bcl10 in B-cell development and LPS response.
    Trends Immunol. (IF 13.000) Pub Date : 2004-03-31
    Klaus-Dieter Fischer,Kerry Tedford,Thomas Wirth

    更新日期:2019-11-01
  • Gob genes, mucus and asthma.
    Trends Immunol. (IF 13.000) Pub Date : 2001-06-29
    L O'Neill

    更新日期:2019-11-01
  • NK cell and DC interactions.
    Trends Immunol. (IF 13.000) Pub Date : 2003-12-31
    Megan A Cooper,Todd A Fehniger,Anja Fuchs,Marco Colonna,Michael A Caligiuri

    Recent interest has focused on interactions between natural killer (NK) cells and dendritic cells (DCs). In vitro and in vivo studies have demonstrated various effects of NK-DC interactions, including activation and cytokine production, maturation of DCs and NK-cell lysis of certain autologous DCs. These interactions are important during an immune response in vivo, however, it remains unclear where in the body NK cells and DCs might interact and whether observed in vitro crosstalk between these cell types happens in vivo. We propose evidence for at least two potential locations of in vivo interactions for human NK cells and DCs, including sites of inflammation and lymph nodes.

    更新日期:2019-11-01
  • The lung as a privileged site for the beneficial actions of PGE2.
    Trends Immunol. (IF 13.000) Pub Date : 2003-12-31
    Carlo Vancheri,Claudio Mastruzzo,Maria Angela Sortino,Nunzio Crimi

    Prostaglandin E2 (PGE2) is commonly considered a potent proinflammatory mediator and is involved in several inflammatory diseases. In the lung, as opposed to many other parts of the body, PGE2 has a role in limiting the immune-inflammatory response as well as tissue repair processes. Understanding the full implications of the regulatory role of PGE2 and how beneficial processes, such as inflammation and tissue repair, become dysregulated to the point of causing disease, might disclose new perspectives in the treatment of pulmonary diseases.

    更新日期:2019-11-01
  • Adenosine: an endogenous regulator of innate immunity.
    Trends Immunol. (IF 13.000) Pub Date : 2003-12-31
    György Haskó,Bruce N Cronstein

    Although inflammatory and immunological reactions protect the host from invasion by microorganisms and eliminate debris at sites of tissue injury, they can also be responsible for significant tissue damage. Thus, regulatory mechanisms that limit damage from an overly exuberant immune response have evolved. It is increasingly apparent that adenosine, a purine nucleoside that is elaborated at injured and inflamed sites, has a central role in the regulation of inflammatory responses and in limiting inflammatory tissue destruction. Adenosine, called a 'retaliatory metabolite' because it is a regulatory autocoid that is generated as a result of cellular injury or stress, interacts with specific G protein-coupled receptors on inflammatory and immune cells to regulate their function. The effects of adenosine, acting at its receptors, on the functions of the cells that mediate innate immune responses, will be reviewed.

    更新日期:2019-11-01
  • The double life of NK receptors: stimulation or co-stimulation?
    Trends Immunol. (IF 13.000) Pub Date : 2003-12-31
    Melissa R Snyder,Cornelia M Weyand,Jörg J Goronzy

    Stimulatory killer immunoglobulin-like receptors, NKG2D and stimulatory receptors of the CD94-NKG2 family have duplicity in function. On natural killer (NK) cells, these receptors act as independent and competent recognition units. Stimulatory NK receptors also appear on subsets of effector T cells, particularly those that have replicated extensively. When expressed on T cells, they amplify signals mediated through the T-cell antigen receptor and, thus, function as co-stimulatory, but not direct stimulatory, molecules. One mechanism responsible for this dichotomy is the differential expression of adaptor molecules. This duplicity in function, which is not seen for other co-stimulatory molecules, is responsible for the unique context information provided by the NK receptors, and it could explain their involvement in chronic inflammation and autoimmunity.

    更新日期:2019-11-01
  • Stressed-out B cells? Plasma-cell differentiation and the unfolded protein response.
    Trends Immunol. (IF 13.000) Pub Date : 2003-12-31
    Jennifer N Gass,Kathryn E Gunn,Rungtawan Sriburi,Joseph W Brewer

    Plasma cells operate as factories where large quantities of Ig heavy and light chains are made and assembled into functional antibodies. The finished products are shipped out with impressive efficiency. A major component of the machinery necessary for high-rate antibody secretion is an elaborate network of endoplasmic reticulum (ER), the site of antibody biosynthesis. Recent discoveries have provided insights into how this expansive secretory machinery is built, equipped and maintained. The unfolded protein response (UPR) pathway, a stress-induced signaling cascade emanating from the ER, regulates the expression and activity of X-box binding protein 1, a transcription factor required for plasma-cell development. The UPR pathway therefore senses conditions in the ER--the very compartment where antibodies are formed--and directs events required for humoral immunity.

    更新日期:2019-11-01
  • On the origins of adaptive immunity: innate immune receptors join the tale.
    Trends Immunol. (IF 13.000) Pub Date : 2003-12-31
    Timo K van den Berg,Jeffrey A Yoder,Gary W Litman

    Among members of the Ig superfamily (IgSF), antigen receptors have the unique capacity to rearrange their variable domains, thereby creating an extensive repertoire for antigen recognition. It is assumed that antigen receptors evolved from a non-rearranging IgSF member by insertion of a transposable element. Although the nature of this predecessor is unknown, two multigene families of innate immune receptors that bear a close structural resemblance to antigen receptor chains have been identified in mammals and bony fish, respectively: signal-regulatory proteins (SIRPs) and novel immune-type receptors (NITRs). Members of both families encode V-set Ig domains with a typical antigen receptor-like joining (J) motif and possess the potential to signal through immunoreceptor tyrosine-based inhibition motifs (ITIMs) or immunoreceptor tyrosine-based activation motifs (ITAMs). By analogy to the T-cell receptor (TCR) and certain innate receptors [e.g. killer cell inhibitory receptors (KIRs)] that recognize MHC molecules, SIRP members regulate immune function by interaction with broadly expressed 'self' ligands. We propose the existence of an evolutionary and functional link between innate and adaptive immune receptors that sheds light on the nature of the antigen receptor predecessor(s).

    更新日期:2019-11-01
  • 更新日期:2019-11-01
  • Inflammation: the link between insulin resistance, obesity and diabetes.
    Trends Immunol. (IF 13.000) Pub Date : 2003-12-31
    Paresh Dandona,Ahmad Aljada,Arindam Bandyopadhyay

    Recent data have revealed that the plasma concentration of inflammatory mediators, such as tumour necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6), is increased in the insulin resistant states of obesity and type 2 diabetes, raising questions about the mechanisms underlying inflammation in these two conditions. It is also intriguing that an increase in inflammatory mediators or indices predicts the future development of obesity and diabetes. Two mechanisms might be involved in the pathogenesis of inflammation. Firstly, glucose and macronutrient intake causes oxidative stress and inflammatory changes. Chronic overnutrition (obesity) might thus be a proinflammatory state with oxidative stress. Secondly, the increased concentrations of TNF-alpha and IL-6, associated with obesity and type 2 diabetes, might interfere with insulin action by suppressing insulin signal transduction. This might interfere with the anti-inflammatory effect of insulin, which in turn might promote inflammation.

    更新日期:2019-11-01
  • Genetic knock out of 60kD Ro (or SSA), a common lupus autoantigen, induces lupus.
    Trends Immunol. (IF 13.000) Pub Date : 2003-12-31
    R Hal Scofield

    Systemic lupus erythematosus (SLE) could have the most complicated phenotype and the most diverse genetics of any genetically complex human disease. Recent research shows that genetic ablation of the gene encoding 60kD Ro, a common autoantigen for SLE patients, results in an SLE-like illness in Ro-/- mice. These data add to the expanding cooperation between mouse and human SLE genetic studies and are the first in which ablation of an autoantigen induces an autoimmune disease.

    更新日期:2019-11-01
  • Towards in silico prediction of immunogenic epitopes.
    Trends Immunol. (IF 13.000) Pub Date : 2003-12-03
    Darren R Flower

    As torrents of new data now emerge from microbial genomics, bioinformatic prediction of immunogenic epitopes remains challenging but vital. In silico methods often produce paradoxically inconsistent results: good prediction rates on certain test sets but not others. The inherent complexity of immune presentation and recognition processes complicates epitope prediction. Two encouraging developments - data driven artificial intelligence sequence-based methods for epitope prediction and molecular modeling methods based on three-dimensional protein structures - offer hope for the future.

    更新日期:2019-11-01
  • Regulation of cytokine signaling by SOCS family molecules.
    Trends Immunol. (IF 13.000) Pub Date : 2003-12-03
    Minoru Fujimoto,Tetsuji Naka

    Cytokine signaling is dependent on the activation of intracellular molecules, including JAKs (Janus family kinases) and STATs (signal transducers and activators of transcription). Since the discovery of the SOCS (suppressor of cytokine signaling) family molecules in 1997, extensive investigation of these molecules has given important insights into the as yet unclarified regulatory mechanisms of cytokine signaling. Recent gene targeting analyses of SOCS molecules have revealed that they do indeed have essential roles in vivo (more specific than those expected from overexpression studies in vitro) in the negative regulation of various cytokines. Moreover, consistent with the pathological actions of cytokines in human diseases, recent lines of evidence also indicate that SOCS molecules are implicated in autoimmunity, allergy and cancers.

    更新日期:2019-11-01
  • Lessons from Nod2 studies: towards a link between Crohn's disease and bacterial sensing.
    Trends Immunol. (IF 13.000) Pub Date : 2003-12-03
    Stephen E Girardin,Jean Pierre Hugot,Philippe J Sansonetti

    Nod2 (Card15) belongs to the family of the recently described Nod molecules, which also includes the closely related protein Nod1 (Card4). Nod proteins have been initially described as intracellular activators of the caspase and NF-kappaB signaling pathways. Recent progress has enabled research to demonstrate genetically that NOD2 (CARD15) is involved in the predisposition to Crohn's disease and Blau syndrome. In addition, biochemical evidence has unraveled the role of Nod1 (Card4) and Nod2 (Card15) as intracellular sensors of bacterial peptidoglycan. Together, studies on Nod2 (Card15) provide a conceptual link between inflammatory disorders, such as Crohn's disease and Blau syndrome, and bacterial sensing.

    更新日期:2019-11-01
  • Induction of tolerogenic DCs: 'you are what you eat'.
    Trends Immunol. (IF 13.000) Pub Date : 2003-12-03
    Karsten Mahnke,Juergen Knop,Alexander H Enk

    Dendritic cells (DCs) take up antigens using antigen receptors that can be divided into three major classes: C-type lectins, integrins and Fc receptors. These receptors facilitate effective presentation of MHC-peptide complexes to T cells, resulting in the induction of immune responses. However, we discuss recent evidence that some receptors also cause induction of tolerance. Signaling motifs within the receptors either block maturation of DCs or induce signals that render DCs tolerogenic. These DCs then either induce regulatory T cells or cause deletion of effector T cells, resulting in the induction of tolerance. Antigen receptors expressed by DCs might therefore have an important role in the induction and maintenance of peripheral tolerance.

    更新日期:2019-11-01
  • Fatty acids as gatekeepers of immune cell regulation.
    Trends Immunol. (IF 13.000) Pub Date : 2003-12-03
    Parveen Yaqoob

    Fatty acids have diverse roles in all cells. They are important as a source of energy, as structural components of cell membranes, as signalling molecules and as precursors for the synthesis of eicosanoids. Recent research has suggested that the organization of fatty acids into distinct cellular pools has a particularly important role in cells of the immune system and that forms of lipid trafficking exist, which are as yet poorly understood. This Review examines the nature and regulation of cellular lipid pools in the immune system, their delivery of fatty acids or fatty acid derivatives to specific locations and their potential role in health and disease.

    更新日期:2019-11-01
  • Regulation of T-cell functions by MHC class II self-presentation.
    Trends Immunol. (IF 13.000) Pub Date : 2003-12-03
    Christian LeGuern

    The role of MHC class II in the control of T-cell responses to self and foreign antigens is still unclear. No unifying principle yet explains how class II molecules repress immunity to self or allogeneic antigens. Our recent data in a model of tolerance to allogeneic grafts, probably induced by allele-specific class II peptides, suggest that it is by presenting themselves [class II peptide(s) docked on self class II, in a complex we have named T-Lo] that class II controls T-cell activity. The engagement of the regulatory T (T-reg)-cell T-cell receptor (TCR) with self T-Lo would explain the beneficial effect of donor-recipient class II matching in clinical transplantation, the correlation between T-cell suppression and class II, and the altered T-reg-cell functions observed in class II-dependent autoimmune pathologies.

    更新日期:2019-11-01
  • The search for the CD8+ cell anti-HIV factor (CAF).
    Trends Immunol. (IF 13.000) Pub Date : 2003-12-03
    Jay A Levy

    Efforts to control HIV infection have led to the development of several antiretroviral drugs that can limit virus replication, however, these therapies do not offer a long-term solution to the infection. We can learn a great deal from HIV-infected individuals who have lived for more than ten years and remain healthy without receiving antiviral drugs. These long-term survivors or long-term non-progressors have an immune system that can control HIV infection. A major component of this immune response is innate immunity, particularly the CD8(+) cell antiviral non-cytotoxic response (CNAR), mediated by a novel CD8(+) cell antiviral factor (CAF). The characteristics of CNAR and CAF will be described and progress made toward identifying CAF will be reviewed. These studies have uncovered several potentially important natural anti-HIV factors and their relationship to the originally described CAF is considered.

    更新日期:2019-11-01
  • TCR triggering: co-receptor-dependent or -independent?
    Trends Immunol. (IF 13.000) Pub Date : 2003-12-03
    Simon J Davis,P Anton van der Merwe

    更新日期:2019-11-01
  • Absence of S100A12 in mouse: implications for RAGE-S100A12 interaction.
    Trends Immunol. (IF 13.000) Pub Date : 2003-12-03
    Georg Fuellen,Dirk Foell,Wolfgang Nacken,Clemens Sorg,Claus Kerkhoff

    更新日期:2019-11-01
  • LAG-3: a regulator of T-cell and DC responses and its use in therapeutic vaccination.
    Trends Immunol. (IF 13.000) Pub Date : 2003-12-03
    Frédéric Triebel

    The function mediated by the engagement of the lymphocyte activation gene-3 (LAG-3, CD223) receptor expressed on activated T cells by its MHC class II ligand has remained enigmatic, partly owing to discrepancies between published results in human and mouse systems. Recent studies in mice have reconciled previous interpretations and clearly show that, as in human cells, LAG-3 negatively regulates T-cell function and homeostasis. As a soluble molecule, LAG-3 activates antigen-presenting cells through MHC class II signalling, leading to increased antigen-specific T-cell responses in vivo.

    更新日期:2019-11-01
  • Tetraspanins: molecular organisers of the leukocyte surface.
    Trends Immunol. (IF 13.000) Pub Date : 2003-11-05
    Jacqueline M Tarrant,Lorraine Robb,Annemiek B van Spriel,Mark D Wright

    Tetraspanins are a large superfamily of cell surface membrane proteins characterised by their four transmembrane domains. They are expressed in a wide variety of cell types and have functional roles in processes, such as cellular adhesion, motility, activation and tumour invasion. Leukocytes express

    更新日期:2019-11-01
  • NK cells and the tumour microenvironment: implications for NK-cell function and anti-tumour activity.
    Trends Immunol. (IF 13.000) Pub Date : 2003-11-05
    Per A Albertsson,Per H Basse,Marianne Hokland,Ronald H Goldfarb,J Fred Nagelkerke,Ulf Nannmark,Peter J K Kuppen

    Although it is clear that natural killer (NK) cells have the ability to recognize and kill tumour cells in vitro, their potential as a highly effective treatment for tumours has not yet been realized in the clinical setting. Following activation, endogenous and adoptively transferred NK cells can be found in tumours. However, not all tumours are equally well-infiltrated, and many of the infiltrating cells do not make target-cell contact but rather reside in the tumour stroma. New insights into the migration of NK cells, their activation status and production of matrix-degrading proteases might help to overcome this localization defect, with implications for the treatment of human cancer.

    更新日期:2019-11-01
  • The genetics of human systemic lupus erythematosus.
    Trends Immunol. (IF 13.000) Pub Date : 2003-11-05
    Betty P Tsao

    Genetic dissection of human systemic lupus erythematosus (SLE) has been under intense studies during the past decade. Although the complexity inherent to polygenic, multifactorial diseases is challenging, several new insights have been obtained in the past several years using linkage and association studies of families containing SLE patients as well as case-control studies of populations. In addition, recent advances in our understanding of the human genome and emerging technology have been providing new tools in analyses of complex traits, such as SLE. An overview of our current understanding of the genetic basis of SLE and a brief review of findings of linkage and association studies are described here.

    更新日期:2019-11-01
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