Role of the NF- κB system in context-specific tuning of the inflammatory gene response.
Role of the NF-κB system in context-specific tuning of the inflammatory gene response. Curr Opin Immunol. 2020 Sep 05;68:21-27 Authors: Chawla M, Roy P, Basak S Abstract The canonical NF-κB pathway instructs the expression of inflammatory genes by the RelA:p50 transcription factor in response to diverse cell-activating stimuli. However, this mainstay RelA:p50 transcriptional output must also be curated so as to provide for stimulus-type-specific and cell-type-specific inflammatory responses adapted to the local tissue-microenvironment. Here, we summarize the fundamental mechanisms regulati...
Source: Current Opinion in Immunology - September 5, 2020 Category: Allergy & Immunology Authors: Chawla M, Roy P, Basak S Tags: Curr Opin Immunol Source Type: research

A unifying hypothesis on the central role of reactive oxygen species in bacterial pathogenesis and host defense in C. elegans.
Abstract During intestinal infection, microbes induce ROS by various mechanisms in C. elegans. ROS can have beneficial roles, acting as antimicrobials and as signaling molecules that activate cytoprotective pathways. Failure to maintain appropriate levels of ROS causes oxidative stress and cellular damage. This review uses the Damage Response Framework to interpret several recent observations on the relationships between infection, host response, and host damage, with a focus on mechanisms mediated by ROS. We propose a unifying hypothesis that ROS drive a collapse in proteostasis in infected C. elegans, which resu...
Source: Current Opinion in Immunology - September 5, 2020 Category: Allergy & Immunology Authors: Goswamy D, Irazoqui JE Tags: Curr Opin Immunol Source Type: research

Leishmania Viannia guyanensis, LRV1 virus and extracellular vesicles: a dangerous trio influencing the faith of immune response during muco-cutaneous leishmaniasis.
Abstract Parasites of Leishmania genus have developed various strategies to overcome host immune response favoring its infection and development toward leishmaniasis. With an array of virulence factors, those parasites modify host macrophage signaling and functions. Depending of the species involved, visceral or cutaneous leishmaniasis will develop. Several years ago, Leishmania Viannia guyanensis that is naturally infected with the endosymbiotic virus Leishmania RNA Virus 1 was found to cause a particularly aggressive form of South-American mucocutaneous leishmaniasis. This virus, when co-transmitted with the par...
Source: Current Opinion in Immunology - August 30, 2020 Category: Allergy & Immunology Authors: Olivier M, Zamboni DS Tags: Curr Opin Immunol Source Type: research

Sensing and clearance of apoptotic cells.
Abstract Macrophages specifically engulf apoptotic cells but not healthy cells. Phosphatidylserine (PtdSer) is localized at the inner leaflet of plasma membranes as a result of the action of flippases (ATP11A and 11C). When cells undergo apoptosis, caspase 3 cleaves and inactivates the flippases, while simultaneously cleaving XKR8 to activate its phospholipid scramblase activity. PtdSer is thus swiftly and irreversibly exposed to the cell surface as an 'eat me' signal. Tissue resident macrophages recognize the apoptotic cells using a PtdSer-receptor TIM4 and engulf them with TAM tyrosine-kinase receptors, and inte...
Source: Current Opinion in Immunology - August 24, 2020 Category: Allergy & Immunology Authors: Nagata S, Segawa K Tags: Curr Opin Immunol Source Type: research

The host targeting effect of chloroquine in malaria.
Abstract Due to the rapid onset and spread of the COVID-19 pandemic, the treatment of COVID-19 patients by hydroxychloroquine alone or in combination with other drugs has captured a great deal of attention and triggered considerable debate. Historically, the worldwide use of quinoline based-drugs has led to a spectacular reduction in death from malaria. Unfortunately, scientists have been forced to seek alternative drugs to treat malaria due to the emergence of chloroquine-resistant parasites in the 1960s. The repurposing of hydroxychloroquine against viral infections, various types of cancer and autoimmune diseas...
Source: Current Opinion in Immunology - August 18, 2020 Category: Allergy & Immunology Authors: Coban C Tags: Curr Opin Immunol Source Type: research

New Treg cell-based therapies of autoimmune diseases: towards antigen-specific immune suppression.
Abstract Naturally occurring FoxP3+CD4+ regulatory T (Treg) cells indispensable for the maintenance of immunological self-tolerance and homeostasis are instrumental in treating autoimmune and other immunological disorders. Stable function of natural Treg cells requires not only the expression of Foxp3 and other Treg signature genes such as CD25 and CTLA-4 but also the generation of Treg-specific epigenetic changes, especially Treg-specific DNA hypomethylation, at these gene loci. Recent studies have shown that the Treg-specific transcriptional and epigenetic changes can be induced in antigen-specific conventional ...
Source: Current Opinion in Immunology - August 18, 2020 Category: Allergy & Immunology Authors: Mikami N, Kawakami R, Sakaguchi S Tags: Curr Opin Immunol Source Type: research

Transcriptional and translational control of Foxp3+ regulatory T cell functional adaptation to inflammation.
Abstract Foxp3+ regulatory T (Treg) cells are the major gatekeepers of the immune system for the maintenance of self-tolerance and immune homeostasis. Treg cell development rests on the key activities of the master-switch transcription factor, Foxp3, which establishes the essential core program that defines Treg cell lineage identity in the thymus and peripheral tissues. Moreover, Foxp3+ Treg cells integrate a variety of inflammatory signals from the tissue microenvironment to engage specialized pathways in order to adapt their suppressive functions in situ. CD4 + Treg cell subsets possess mechanisms...
Source: Current Opinion in Immunology - August 17, 2020 Category: Allergy & Immunology Authors: Piccirillo CA Tags: Curr Opin Immunol Source Type: research

The Ins and Outs of TAPBPR.
Abstract Peptide presentation on MHC class I molecules (MHC-I) is central to mounting effective antiviral and antitumoral immune responses. The tapasin-related protein TAPBPR is an MHC-I peptide editor which shapes the final peptide repertoire displayed on the cell surface. Here, we review recent findings which further elucidate the mechanisms by which TAPBPR performs peptide editing on a molecular level, and how glycosylation on MHC-I influences the interaction with TAPBPR and the peptide loading complex. We also explore how the function of TAPBPR can be utilized to promote exogenous peptide loading directly onto...
Source: Current Opinion in Immunology - August 16, 2020 Category: Allergy & Immunology Authors: Ilca T, Boyle LH Tags: Curr Opin Immunol Source Type: research

Control of regulatory T cell homeostasis.
Abstract CD4+ Foxp3+ T Regulatory (Treg) cells play a critical role in the homeostasis and maintenance of the immune system. The understanding of different aspects of Treg cells biology remains an intensively investigated subject as altering their generation, stability, or function by drugs or biologics may have therapeutic value in the treatment of autoimmune and inflammatory diseases as well as cancers. This review will focus on recent studies on the role of cytokines, T Cell Receptor (TCR) and co-stimulatory/co-inhibitory molecules signaling, location and metabolism on the homeostasis and stability of Treg cell...
Source: Current Opinion in Immunology - August 15, 2020 Category: Allergy & Immunology Authors: Buszko M, Shevach EM Tags: Curr Opin Immunol Source Type: research

Immunometabolism and autoimmunity.
Abstract Over the last few years, immune cell metabolism has become one of the most stimulating areas of investigation in the field of immunology. Compelling evidence has revealed that metabolic pathways are closely associated to cell functions and immune cells adopt defined metabolic programs to sustain their activity and respond to micro-environmental demands. It is now clear that alterations in cell metabolism can favour dysregulation typical of autoreactive immune cells, thus sustaining loss of immunological self-tolerance. In this short review, we highlight the main metabolic alterations associated with both ...
Source: Current Opinion in Immunology - August 8, 2020 Category: Allergy & Immunology Authors: Galgani M, Bruzzaniti S, Matarese G Tags: Curr Opin Immunol Source Type: research

Dissecting the antibody-OME: past, present, and future.
Abstract Humoral immunity is key to protection for nearly all licensed vaccines. Yet, the design of vaccines has been more difficult for some of our most deadly killers (e.g. HIV, influenza, Dengue virus, etc.), likely due to our incomplete understanding of the precise immunological mechanisms associated with protection. Humoral immunity is governed both by B-cells and their bi-functional secreted antibodies, all of which have a unique capacity to evolve during an immune response. Current OMIC technologies capture individual features of the humoral immune response, providing a glimpse into humoral components (Fab/...
Source: Current Opinion in Immunology - August 2, 2020 Category: Allergy & Immunology Authors: Loos C, Lauffenburger DA, Alter G Tags: Curr Opin Immunol Source Type: research

Understanding immune variation for improved translational medicine.
Abstract The goal of translational medicine is to use an improved understanding of human biology to develop new clinical approaches. Immune responses are highly variable from one person to another, with this variability strongly impacting clinical outcome. Variable immunity can determine differential risks for infection, for development of autoimmunity, and for response to therapeutic interventions. Therefore, a better understanding of the causes of such differences has huge potential to improve patient management through precision medicine strategies. Variability in immunity is determined by intrinsic (e.g. age, ...
Source: Current Opinion in Immunology - July 31, 2020 Category: Allergy & Immunology Authors: Duffy D Tags: Curr Opin Immunol Source Type: research

Systems immunology.
Abstract Systems biological approaches to immunology have grown exponentially in the past decade, especially as broad approaches to data collection have become more accessible. It is still in its infancy; however, largely descriptive, and looking for the main drivers of particular phenomena, such as vaccination effects or pregnancy. But this lays the ground work for an increasingly sophisticated appreciation of subsystems and interactions and will lead to predictive modeling and a deeper understanding of human diseases and interactions with pathogens. PMID: 32738786 [PubMed - as supplied by publisher] (Source...
Source: Current Opinion in Immunology - July 29, 2020 Category: Allergy & Immunology Authors: Davis MM Tags: Curr Opin Immunol Source Type: research

Deciphering flavivirus-host interactions using quantitative proteomics.
We describe new findings on our understanding of how flaviviruses impact protein-protein interactions, protein-RNA interactions, protein abundance, and post-translational modifications to modulate viral infection. PMID: 32682290 [PubMed - as supplied by publisher] (Source: Current Opinion in Immunology)
Source: Current Opinion in Immunology - July 15, 2020 Category: Allergy & Immunology Authors: Li M, Ramage H, Cherry S Tags: Curr Opin Immunol Source Type: research

Bacteria-immune cells dialog and the homeostasis of the systems.
Abstract The dialog between microbes and immune cells is critical for the establishment and maintenance of immune homeostasis. Bacterial-derived metabolites or structural components initiate immune signaling pathways and transcriptional factors, inducing a broad range of specificities and functional repertoires of the immune cells. Conversely, the immune system regulates the composition and function of bacterial communities. Elements of the adaptive immunity, including maternal antibodies and mucosal antibody responses, play crucial roles in protecting the hosts from pathogens in addition to promoting colonization...
Source: Current Opinion in Immunology - July 13, 2020 Category: Allergy & Immunology Authors: Guzman-Bautista ER, Suzuki K, Asami S, Fagarasan S Tags: Curr Opin Immunol Source Type: research

Dissecting genetic determinants of variation in human immune responses.
Abstract The immune system is paradigmatic for a complex arrangement of heterogenous cells performing distinct, frequently temporally and anatomically dissociated, functions. Immune dysfunction is a common characteristic across most diseases and human genetic approaches have revealed that many disease risk loci are associated with expression profiles and counts of specific immune subsets. Furthermore, genetic regulators of immune function may only demonstrate activity in specific disease-linked contexts. Here we explore steps taken to dissect the genetic determinants of variation in immune response across cell cou...
Source: Current Opinion in Immunology - July 4, 2020 Category: Allergy & Immunology Authors: Tong O, Fairfax BP Tags: Curr Opin Immunol Source Type: research

Polymorphisms of HLA-B: influences on assembly and immunity.
Abstract The major histocompatibility class I (MHC-I) complex functions in innate and adaptive immunity, mediating surveillance of the subcellular environment. In humans, MHC-I heavy chains are encoded by three genes: the human leukocyte antigen (HLA)-A, HLA-B, and HLA-C. These genes are highly polymorphic, which results in the expression, typically, of six different HLA class I (HLA-I) proteins on the cell surface, and the presentation of diverse peptide antigens to CD8+ T cells for broad surveillance against many pathogenic conditions. Recent studies of HLA-B allotypes show that the polymorphisms, not surprising...
Source: Current Opinion in Immunology - June 30, 2020 Category: Allergy & Immunology Authors: Olson E, Geng J, Raghavan M Tags: Curr Opin Immunol Source Type: research

Inhibitory receptor agonists: the future of autoimmune disease therapeutics?
Abstract Central and peripheral tolerance both contribute to protection against autoimmunity. The pathogenesis of autoimmunity, however, can result from critical deficits or limitations in peripheral and/or central tolerance mechanisms, presenting an opportunity for therapeutic intervention. Recent advances highlight the substantial impact of inhibitory receptors (IRs), which mediate peripheral tolerance, in autoimmunity. Deletion and blockade studies in mice, IR disruption in humans, and correlation with positive disease outcomes all highlight potential clinical benefits of enhancing IR signaling (agonism)-specif...
Source: Current Opinion in Immunology - June 30, 2020 Category: Allergy & Immunology Authors: Grebinoski S, Vignali DA Tags: Curr Opin Immunol Source Type: research

DRiPs get molecular.
te; J Abstract The defective ribosomal product (DRiP) hypothesis was proposed nearly 25 years ago to account for the rapid generation of peptides from otherwise metabolically stable viral proteins. It posits that errors in converting genetic information into stable proteins accounts for a sizeable fraction of the immunopeptidome. Here, we review recent studies that provide insight into the importance of DRiPs for immunosurveillance and the myriad mechanisms that give rise to DRiPs. PMID: 32615334 [PubMed - as supplied by publisher] (Source: Current Opinion in Immunology)
Source: Current Opinion in Immunology - June 29, 2020 Category: Allergy & Immunology Authors: Yewdell JW, Hollý J Tags: Curr Opin Immunol Source Type: research

An ancient view on host pathogen interaction across time and space.
Abstract The ancient DNA revolution provided diverse fields with an unprecedented opportunity to look back into the past and shed light on research aspects that were until now subject to speculation and inference from modern data. In particular enrichment methods that allow the targeted retrieval of millions of SNP positions from ancient human genomes, or even complete bacterial and viral genomes have the potential to revolutionize our understanding of host pathogen interactions. Ancient DNA combined with new bioinformatic tools now even allows actual allele calling for immunogenetic systems such as Human Leukocyt...
Source: Current Opinion in Immunology - June 27, 2020 Category: Allergy & Immunology Authors: Barquera R, Krause J Tags: Curr Opin Immunol Source Type: research

T cell analysis in vaccination.
Abstract A major problem in the analysis of vaccine candidates is the lack of any agreed upon surrogates of efficacy, which means that for diseases that depend on a strong T cell response (HIV, TB especially) the only option is to perform an efficacy trial, involving thousands of subjects, enormous costs, and years before the results are known [1]. We also know that T cell responses are an important part of most pathogen responses, and so identifying key T cell response metrics in early vaccine trials would be generally useful. Given our ignorance of what the most important variables are, what would we like to mea...
Source: Current Opinion in Immunology - June 27, 2020 Category: Allergy & Immunology Authors: Davis MM Tags: Curr Opin Immunol Source Type: research

MR1: a multi-faceted metabolite sensor for T cell activation.
Abstract The major histocompatibility complex class I-related molecule MR1 captures and presents small metabolites to MR1-restricted T cells including Mucosal Associated Invariant T (MAIT) cells. The first MR1 ligands discovered were intermediates of microbial riboflavin synthesis, antigens presented to alert inflammatory MAIT cells to bacterial infection. Recent advances have expanded the range of MR1 ligands to include extracellular metabolites released by the commensal microbiome, and yet undefined antigens presented by cancer cells to mediate MR1-dependent anti-tumor activity. MR1 thus exhibits a multifaceted ...
Source: Current Opinion in Immunology - June 27, 2020 Category: Allergy & Immunology Authors: McWilliam HE, Villadangos JA Tags: Curr Opin Immunol Source Type: research

The love and hate relationship of HLA-DM/DO in the selection of immunodominant epitopes.
Abstract Successful activation of CD4 T cells is centered around the ability of antigen presenting cells to successfully process, select Class II immunodominant epitopes from exogenous antigens and to present it to cognate T cells. To achieve this, newly synthesized MHC-II molecules are transferred to a specialized compartment which contain both exogenous antigens and the Class II processing machinery. Here in a process known as 'editing,' the Class II accessory molecule DM (HLA-DM human; murine H2-M) facilitates the loading and selection of exogenous peptides to MHC class II molecules thereby assuring proper sele...
Source: Current Opinion in Immunology - June 26, 2020 Category: Allergy & Immunology Authors: Welsh RA, Sadegh-Nasseri S Tags: Curr Opin Immunol Source Type: research

Protective and pathogenic roles for mast cells during viral infections.
Abstract Mast cells (MCs) are long-lived immune cells. They are armed with preformed mediators within granules that can be instantaneously released in response to an invading pathogen, including certain viruses. At the skin and mucosae, they initiate innate immune responses and promote the development of adaptive immune responses, through cellular recruitment or antigen presentation. However, systemic MC activation may promote immune pathologies through their vasoactive proteases and biogenic amines. Recently, MC products were identified to contribute to pathologies associated with viral hemorrhagic fever, such va...
Source: Current Opinion in Immunology - June 18, 2020 Category: Allergy & Immunology Authors: Rathore AP, St John AL Tags: Curr Opin Immunol Source Type: research

Emerging technologies for systems vaccinology - multi-omics integration and single-cell (epi)genomic profiling.
Abstract Systems vaccinology leverages high-throughput 'omics' technologies, such as transcriptomics, metabolomics, and mass cytometry, coupled with computational approaches to construct a global map of the complex processes that occur during an immune response to vaccination. Its goal is to define the mechanisms of protective immunity and to identify cellular and molecular correlates of vaccine efficacy. Emerging technological advances including integration of multi-omics datasets, and single-cell genomic and epigenomic profiling of immune responses, have invigorated systems vaccinology, and provide new insights ...
Source: Current Opinion in Immunology - June 3, 2020 Category: Allergy & Immunology Authors: Wimmers F, Pulendran B Tags: Curr Opin Immunol Source Type: research

The fibroblastic T cell niche in lymphoid tissues.
Abstract Fibroblastic reticular cells (FRCs) are a necessary immunological component for T cell health. These myofibroblasts are specialized for immune cell support and develop in locations where T and B lymphocyte priming occurs, usually secondary lymphoid organs, but also tertiary lymphoid structures and sites of chronic inflammation. This review describes their dual supportive and suppressive functions and emerging evidence on the co-ordination required to balance these competing roles. PMID: 32497868 [PubMed - as supplied by publisher] (Source: Current Opinion in Immunology)
Source: Current Opinion in Immunology - June 1, 2020 Category: Allergy & Immunology Authors: Fletcher AL, Baker AT, Lukacs-Kornek V, Knoblich K Tags: Curr Opin Immunol Source Type: research

Mesothelial cells regulate immune responses in health and disease: role for immunotherapy in malignant mesothelioma.
e GF Abstract The mesothelium when first described was thought to function purely as a non-adhesive surface to facilitate intracoelomic movement of organs. However, the mesothelium is now recognized as a dynamic cellular membrane with many important functions that maintain serosal integrity and homeostasis. For example, mesothelial cells interact with and help regulate the body's inflammatory and immune system following infection, injury, or malignancy. With recent advances in our understanding of checkpoint molecules and the advent of novel immunotherapy approaches, there has been an increase in the number of stu...
Source: Current Opinion in Immunology - May 30, 2020 Category: Allergy & Immunology Authors: Mutsaers SE, Pixley FJ, Prêle CM, Hoyne GF Tags: Curr Opin Immunol Source Type: research

Inflammation following trypanosome infection and persistence in the skin.
Abstract Human African trypanosomes rely for their transmission on tsetse flies (Glossina sp.) that inoculate parasites into the skin during blood feeding. The absence of a protective vaccine, limited knowledge about the infection immunology, and the existence of asymptomatic carriers sustaining transmission are major outstanding challenges towards elimination. All these relate to the skin where (i) parasites persist and transmit to tsetse flies and (ii) a successful vaccination strategy should ideally be effective. Host immune processes and parasite strategies that underlie early infection and skin tropism are es...
Source: Current Opinion in Immunology - May 20, 2020 Category: Allergy & Immunology Authors: Mabille D, Caljon G Tags: Curr Opin Immunol Source Type: research

Food allergy: epidemiology, pathogenesis, diagnosis, prevention, and treatment.
Abstract Food allergy affects up to 10% of the population. The identification of modifiable risk factors including skin barrier dysfunction, vitamin D deficiency, microbiome, and route and timing of allergen exposure is leading to effective prevention strategies, and some of which are now included in public health guidelines. An increasing understanding of the pathophysiology has improved diagnostic options and revealed novel manifestations such as delayed anaphylaxis to mammalian meat related to sensitization to a sugar moiety triggered by tick bites. Current diagnosis has improved with the commercialization of a...
Source: Current Opinion in Immunology - May 19, 2020 Category: Allergy & Immunology Authors: Lopes JP, Sicherer S Tags: Curr Opin Immunol Source Type: research

Commensal bacteria in the upper respiratory tract regulate susceptibility to infection.
Abstract The human body is host to several distinct microbial communities. Disruption of these communities increases susceptibility to a wide range of diseases, including respiratory tract infections. While commensal bacteria in the gut contribute to this effect, recent studies point to a role for commensals occupying the upper respiratory tract through direct pathogen killing and by modifying nasal and lung immune homeostasis. Clinical trials exploring 'probiotic' respiratory tract commensals are an exciting development in this area. Upper respiratory tract microbiome sequencing has revealed that destabilization ...
Source: Current Opinion in Immunology - May 13, 2020 Category: Allergy & Immunology Authors: Clark SE Tags: Curr Opin Immunol Source Type: research

Cancer-associated fibroblasts: key determinants of tumor immunity and immunotherapy.
te; E Abstract Immune-targeted approaches are rapidly changing the therapeutic landscape for cancer. In spite of that, most patients show resistance or acquire resistance to these therapies. Increasing work describing the tumor microenvironment (TME) has highlighted this space as one of the key determinants in tumor immune response and immunotherapeutic success. Frequently overlooked within this space, cancer-associated fibroblasts (CAFs) within the TME have surfaced as an important dictator of the tumor immune response. Herein, we review recent advances in defining the role of CAF-immune cell interactions in soli...
Source: Current Opinion in Immunology - May 10, 2020 Category: Allergy & Immunology Authors: Barrett R, Puré E Tags: Curr Opin Immunol Source Type: research

Structural and dynamic studies of TAPBPR and Tapasin reveal the mechanism of peptide loading of MHC-I molecules.
Abstract Major histocompatibility complex encoded class I (MHC-I) molecules bind a broad spectrum of peptides generated in the cytoplasm and encountered during protein folding and maturation in the endoplasmic reticulum (ER). For cell surface expression and recognition by T cell receptors (TCR) and natural killer (NK) receptors, MHC-I require loading with high affinity peptides. Peptide optimization is catalyzed by either of two pathways. The first is via the peptide-loading complex (PLC) which consists of the transporter associated with antigen processing (TAP)1/TAP2 heterodimer, tapasin (an ER resident chaperone...
Source: Current Opinion in Immunology - May 8, 2020 Category: Allergy & Immunology Authors: Margulies DH, Jiang J, Natarajan K Tags: Curr Opin Immunol Source Type: research

Virus-encoded cytokine and chemokine decoy receptors.
te; A Abstract Poxviruses and herpesviruses encode secreted versions of cytokine receptors as a unique strategy to evade the host immune response. Recent advances in the field have shown the great impact of some of these proteins in immune modulation and viral pathogenesis, and have uncovered unique properties of these viral proteins not found in the cellular counterparts. These modifications inspired by viruses lead to improved immune modulatory activity of the soluble cytokine receptors, information that has been used to develop more efficient therapeutics to treat inflammatory conditions. PMID: 32408109 [P...
Source: Current Opinion in Immunology - May 8, 2020 Category: Allergy & Immunology Authors: Hernaez B, Alcamí A Tags: Curr Opin Immunol Source Type: research

Mesenchymal perivascular cells in immunity and disease.
Abstract The mesenchymal microenvironment is increasingly recognized as a major player in immunity. Here we focus on mesenchymal cells located within or in proximity to the blood vessels wall, which include pericytes, adventitial fibroblasts and mesenchymal stromal cells. We discuss recent evidence that these cells play a role in tissue homeostasis, immunity and inflammatory pathologies by multiple mechanisms, including vascular modulation, leucocyte migration, activation or survival in the perivascular space and differentiation into specialized 'effector' mesenchymal cells essential for tissue repair and immunity...
Source: Current Opinion in Immunology - May 5, 2020 Category: Allergy & Immunology Authors: Benabid A, Peduto L Tags: Curr Opin Immunol Source Type: research

Dendritic cells and the skin environment.
Abstract The skin is inhabited by several immune cell populations that serve as a first line of defence against pathogen invasion. Amongst these populations are dendritic cells, which play an essential sentinel function by taking up antigen or infectious agents and transporting them to the lymph node for T cell recognition and the priming of immune responses. In this review, we briefly summarise recent advances showing how skin dendritic cells are connected to a network of epithelial and stromal cells, which provide structural support, growth factors, spatial cues, contact with the external environment and the ski...
Source: Current Opinion in Immunology - May 5, 2020 Category: Allergy & Immunology Authors: Ronchese F, Hilligan KL, Mayer JU Tags: Curr Opin Immunol Source Type: research

Fibroblast subtypes in tissues affected by autoimmunity: with lessons from lymph node fibroblasts.
Abstract The recent advent of single-cell technologies has fast-tracked the discovery of multiple fibroblast subsets in tissues affected by autoimmune disease. In recent years, interest in lymph node fibroblasts that support and regulate immune cells has also grown, leading to an expanding framework of stromal cell subsets with distinct spatial, transcriptional, and functional characteristics. Inflammation can drive tissue fibroblasts to adopt a lymphoid tissue stromal cell phenotype, suggesting that fibroblasts in diseased tissues can have counterparts in lymphoid tissues. Here, we examine fibroblast subsets in t...
Source: Current Opinion in Immunology - May 5, 2020 Category: Allergy & Immunology Authors: Shipman WD, Sandoval MJ, Veiga K, Donlin LT, Lu TT Tags: Curr Opin Immunol Source Type: research

Improving efficacy of glycoconjugate vaccines: from chemical conjugates to next generation constructs.
Abstract Glycoconjugate vaccines are among the safest and most successful vaccines developed during the past 30 years. Since the first semisynthetic chemical conjugate vaccine licensed in the 1980's to protect human against Haemophilus influenzae type b infection, conjugate vaccines against Neisseria meningitidis and Streptococcus pneumoniae have been developed and registered using the same approach (i.e. bacterial growth to produce capsular polysaccharide antigen and chemical coupling to carrier protein). Other types of conjugate vaccines have been recently developed and tested in clinical trials, prepared by cou...
Source: Current Opinion in Immunology - April 30, 2020 Category: Allergy & Immunology Authors: Berti F, Micoli F Tags: Curr Opin Immunol Source Type: research

HBV as a target for CAR or TCR-T cell therapy.
Abstract Engineering HBV-specific T cells utilizing a chimeric antigen receptor (CAR) or a classical T cell receptor (TCR) provides a well characterized, sizeable and functionally intact population of HBV-specific T cells with identical in vitro functionality to the T cells isolated in patients who resolved acute HBV infection. In this review we present evidences of the virological and immunological features of chronic HBV infection, alone or in combination with Hepatitis Delta that might make it amenable for CAR/TCR-T cells therapy. PMID: 32361634 [PubMed - as supplied by publisher] (Source: Current Opinion in Immunology)
Source: Current Opinion in Immunology - April 30, 2020 Category: Allergy & Immunology Authors: Bertoletti A, Tan AT Tags: Curr Opin Immunol Source Type: research

FALC stromal cells define a unique immunological niche for the surveillance of serous cavities.
cute;zech C Abstract The serous cavities contain specialised adipose tissues which house small clusters of immune cells known as fat-associated lymphoid clusters (FALCs). The continuous flow of fluid from the serous cavities through FALCs makes them unique niches for the clearance of fluid phase contaminants and initiation of locally protective immune responses during infection and inflammation. Development, and activation of FALCs both at homeostasis and following inflammation are co-ordinated by the close interaction of mesothelial and fibroblastic stromal cell populations with immune cells. In this review we di...
Source: Current Opinion in Immunology - April 27, 2020 Category: Allergy & Immunology Authors: Jackson-Jones LH, Bénézech C Tags: Curr Opin Immunol Source Type: research

Co-evolution of mutagenic genome editors and vertebrate adaptive immunity.
Abstract The adaptive immune systems of all vertebrates rely on self-DNA mutating enzymes to assemble their antigen receptors in lymphocytes of their two principal lineages. In jawed vertebrates, the RAG1/2 recombinase directs V(D)J recombination of B cell and T cell receptor genes, whereas the activation-induced cytidine deaminase AID engages in their secondary modification. The recombination activating genes (RAG) 1 and 2 evolved from an ancient transposon-encoded genome modifier into a self-DNA mutator serving adaptive immunity; this was possible as a result of domestication, involving several changes in RAG1 a...
Source: Current Opinion in Immunology - April 27, 2020 Category: Allergy & Immunology Authors: Trancoso I, Morimoto R, Boehm T Tags: Curr Opin Immunol Source Type: research

Immune outposts in the adventitia: One foot in sea and one on shore.
Abstract Advances in microscopy, genetically modified mice, and single-cell RNA sequencing have begun to deconvolute the composition and function of tissue immune niches. Here we discuss the evidence that the adventitia, the outermost layer of larger blood vessels, is a conserved niche and tissue immune outpost for multiple immune cells, including group 2 innate lymphoid cells (ILC2) and subsets of tissue-resident memory T cells, macrophages, and dendritic cells. We also describe the unique non-immune composition at adventitial regions, including fibroblast-like stromal cell subsets, lymphatic and blood endothelia...
Source: Current Opinion in Immunology - April 24, 2020 Category: Allergy & Immunology Authors: Cautivo KM, Steer CA, Molofsky AB Tags: Curr Opin Immunol Source Type: research

Technologies for assessing vaccine responses in the very young.
Abstract Many vaccines are administered to young children in order to prevent infectious diseases early in life. At the same time, most of these vaccines are not developed specifically with the immune system of young children in mind and our understanding of how newborn immune systems differ from adult counterparts is incomplete. The main reason for this lack of understanding stems from the ethical and logistical difficulties in obtaining samples from young children as well as the challenges associated with the small volume samples available. Here I review some recent developments made in this field and discuss th...
Source: Current Opinion in Immunology - April 24, 2020 Category: Allergy & Immunology Authors: Brodin P Tags: Curr Opin Immunol Source Type: research

Stromal cells and immune cells involved in formation of lymph nodes and their niches.
Abstract Secondary lymphoid organs are critical for efficient interaction between innate antigen presenting cells and adaptive lymphocytes in order to start adaptive immune responses. The efficiency by which these cellular subsets meet is highly increased by the orchestrating role of stromal cells within the secondary lymphoid organs. These cells provide cytokines, chemokines and cell surface receptors necessary for survival and guided migration. This increases the likelihood that antigen specific adaptive immune responses occur. Already from initial formation of secondary lymphoid organs, the interaction of immun...
Source: Current Opinion in Immunology - April 20, 2020 Category: Allergy & Immunology Authors: Koning JJ, Mebius RE Tags: Curr Opin Immunol Source Type: research

Stromal cell control of conventional and ectopic germinal centre reactions.
Abstract The germinal centre (GC) is a specialized cellular structure that forms in response to antigenic stimulation. It generates long-term humoral immunity through the production of memory B cells and long-lived antibody-secreting plasma cells. Conventional GCs form within secondary lymphoid organs, where networks of specialised stromal cells that form during embryogenesis act as the stage upon which the various GC immune cell players are brought together, nurtured and co-ordinated to generate a productive response. In non-lymphoid organs, ectopic GCs can form in response to persistent antigenic and inflammator...
Source: Current Opinion in Immunology - April 20, 2020 Category: Allergy & Immunology Authors: Silva-Cayetano A, Linterman MA Tags: Curr Opin Immunol Source Type: research

Microbiota-immune interactions in asthma pathogenesis and phenotype.
Abstract The complexity and the mechanistic role of microbial communities at mucosal surfaces are only now beginning to be understood. Their impact on host metabolism, development, and immune responses to infectious and inert stimuli may be centrally linked to the metabolic functions of these communities within the established microbiome. The structure and function of microbial communities are influenced both early and throughout life by many environmental factors, exposures, diet, and disease. Understanding how the microbiome influences the host during health is likely just as important as understanding how it in...
Source: Current Opinion in Immunology - April 19, 2020 Category: Allergy & Immunology Authors: Lukacs NW, Huang YJ Tags: Curr Opin Immunol Source Type: research

Recent advances in atopic dermatitis.
Abstract The prevalence and disease burden of atopic dermatitis (AD) is substantial. AD causes significant impairment in quality of life. It is also associated with mental disorders as well as cardiovascular diseases. Many factors including race, environment, skin barrier dysfunction, immune regulatory abnormalities, and microbiome have been reported to affect the pathophysiology of AD. A variety of cell types including Th2, Th17, Th22, and type 2 innate lymphoid cells contribute to AD. Cytokines from these immune cells cause abnormal epidermal differentiation and skin barrier dysfunction. Moreover, microbial dysb...
Source: Current Opinion in Immunology - April 13, 2020 Category: Allergy & Immunology Authors: Ahn K, Kim BE, Kim J, Leung DY Tags: Curr Opin Immunol Source Type: research

Aspirin-exacerbated respiratory disease.
Abstract Aspirin-exacerbated respiratory disease (AERD) classically presents with severe asthma, nasal polyposis, and respiratory exacerbations in response to cyclooxygenase (COX)-1 inhibition. Recent advances in our understanding of AERD have revealed multiple facets of immune dysregulation, including diminished prostaglandin E2 (PGE2) function and elevated levels of both cysteinyl leukotrienes (CysLTs) and innate cytokines such as interleukin 33 (IL-33). Inflammatory mediators in AERD heighten the recruitment and activation of innate lymphoid cells type 2 (ILC2), mast cells, eosinophils, and platelet-adherent le...
Source: Current Opinion in Immunology - April 13, 2020 Category: Allergy & Immunology Authors: Wangberg H, White AA Tags: Curr Opin Immunol Source Type: research

Immunotherapy in allergic diseases - improved understanding and innovation for enhanced effectiveness.
Abstract Allergen immunotherapy leads to tolerance through multiple mechanisms that include tolerogenic dendritic cells and T and B regulatory cells. These induced cellular populations produce mediators to skew the immune response to a tolerogenic milieu that, among others, results in IgG4 blocking antibodies formation and lowered FcE receptors. All lead in decreased effector responses from mast cells, eosinophils, and basophils thus limiting the allergic inflammation. Clinically, this results in better allergic rhinitis control and, of importance, asthma prevention. Newer approaches include modified allergens, se...
Source: Current Opinion in Immunology - April 6, 2020 Category: Allergy & Immunology Authors: Mitsias DI, Xepapadaki P, Makris M, Papadopoulos NG Tags: Curr Opin Immunol Source Type: research

CD4+ teff cell heterogeneity: the perspective from single-cell transcriptomics.
Abstract Single-cell transcriptomics (scRNAseq) holds the promise to generate definitive atlases of cell types. We review scRNAseq studies of conventional CD4+ αβ T cells performed in a variety of challenged contexts (infection, tumor, allergy) that aimed to parse the complexity and representativity of previously defined CD4+ T cell types, lineages, and cosmologies. With a few years' experience, the field has realized the difficulties and pitfalls of scRNAseq. With the very high-dimensionality of scRNAseq data, subset definitions based on low-dimensionality marker combinations tend to fade or blur: cell...
Source: Current Opinion in Immunology - April 4, 2020 Category: Allergy & Immunology Authors: Zemmour D, Kiner E, Benoist C Tags: Curr Opin Immunol Source Type: research

DNA vaccines: prime time is now.
Abstract Recently newer synthetic DNA vaccines have been rapidly advanced to clinical study and have demonstrated an impressive degree of immune potency and tolerability. Improvements in DNA delivery over prior needle and syringe approaches include jet delivery, gene gun delivery, among others. Among the most effective of these new delivery methods, advanced electroporation (EP), combined with other advances, induces robust humoral and cellular immunity in both preventative as well as therapeutic studies. Advancements in the design of the DNA inserts include leader sequence changes, RNA and codon optimizations, im...
Source: Current Opinion in Immunology - April 4, 2020 Category: Allergy & Immunology Authors: Gary EN, Weiner DB Tags: Curr Opin Immunol Source Type: research