All along the watchtower: group 2 innate lymphoid cells in allergic responses.
Abstract Group 2 innate lymphoid cells (ILC2) are a subset of innate lymphocytes that responds to local, tissue-derived signals and initiates allergic immune responses. ILC2 activation promotes the recruitment of eosinophils, polarization of alternatively activated macrophages, and tissue-remodeling, processes associated with the 'weep and sweep' response to helminthic worm colonization and infection. ILC2s also coordinate both physiologic and pathologic type 2 allergic immune responses, including promoting normal tissue development and remodeling and driving allergic pathology such as atopic dermatitis and allerg...
Source: Current Opinion in Immunology - May 31, 2018 Category: Allergy & Immunology Authors: Dahlgren MW, Molofsky AB Tags: Curr Opin Immunol Source Type: research

Dendritic cells, T cells and lymphatics: dialogues in migration and beyond.
l;rster R Abstract Immune cells continuously recirculate through lymph vessels en route from peripheral tissues to the blood. Leuyte trafficking into and within lymph vessels is mediated by an interply with lymphatic endothelial cells (LECs). However, lymphatic vessels are much more than mere conduits for fluid and immune cell transport. Data accumulating during past several years indicate that LECs support T cell survival, induce tolerance to self-antigens, inhibit exaggerated T cell proliferation during immune response and maintain T cell memory. Reciprocally, leukocytes impact LEC biology: lymphatic vessel perm...
Source: Current Opinion in Immunology - May 29, 2018 Category: Allergy & Immunology Authors: Permanyer M, Bošnjak B, Förster R Tags: Curr Opin Immunol Source Type: research

Helminth-induced regulatory T cells and suppression of allergic responses.
Abstract Infection with helminths has been associated with lower rates of asthma and other allergic diseases. This has been attributed, in part, to the ability of helminths to induce regulatory T cells that suppress inappropriate immune responses to allergens. Recent compelling evidence suggests that helminths may promote regulatory T cell expansion or effector functions through either direct (secretion of excretory/secretory molecules) or indirect mechanisms (regulation of the microbiome). This review will discuss key findings from human immunoepidemiological observations, studies using animal models of disease, ...
Source: Current Opinion in Immunology - May 28, 2018 Category: Allergy & Immunology Authors: Logan J, Navarro S, Loukas A, Giacomin P Tags: Curr Opin Immunol Source Type: research

From fish embryos to human patients: lymphangiogenesis in development and disease.
Abstract The lymphatic vasculature plays vital roles in immune surveillance, fluid homeostasis and fat absorption in the body. Lined by endothelial cells, the lymphatic system is functionally distinct from the blood vasculature, and fulfills different physiological functions. In recent years, insight from zebrafish, mice and human patients have improved our understanding of lymphatics, and the interplay between zebrafish genetics, studies in mice and GWAS analysis in human patients have identified genes that, when mutated, will lead to lymphedema formation. Here, we focus on components of the Vegfr3 pathway, and h...
Source: Current Opinion in Immunology - May 22, 2018 Category: Allergy & Immunology Authors: Mauri C, Wang G, Schulte-Merker S Tags: Curr Opin Immunol Source Type: research

Historical overview of lymphangiogenesis.
Abstract The investigation of the lymphatic system has a very long and intriguing history, with several medical figures which brought important contributions. Work on the lymphatic system began in the 17th century, and by the beginning of the 19th century the anatomy of most of the lymphatic system had been described. This system is an essential component of the immune system, as well as vital to the maintenance of fluid homeostasis within the body. In this review article, I summarize the most important contributions to this field, until to the discovery of a specific lymphangiogenic factor, namely vascular endoth...
Source: Current Opinion in Immunology - May 19, 2018 Category: Allergy & Immunology Authors: Ribatti D Tags: Curr Opin Immunol Source Type: research

Innate effector cells in angiogenesis and lymphangiogenesis.
Abstract Angiogenesis and lymphangiogenesis are distinct and complex processes requiring a finely tuned balance between stimulatory and inhibitory signals. During adulthood, angiogenesis and lymphangiogenesis are activated at sites of tumor growth, tissue injury and remodeling, and chronic inflammation. Vascular endothelial growth factors (VEGFs), angiopoietin (ANGPTs) and a multitude of additional signaling molecules play distinct roles in the modulation of angiogenesis/lymphangiogenesis. VEGFs and ANGPTs activate specific tyrosine kinase receptor (e.g., VEGFR1, VEGFR-2, VEGFR-3 and TIE2 respectively), expressed ...
Source: Current Opinion in Immunology - May 17, 2018 Category: Allergy & Immunology Authors: Varricchi G, Loffredo S, Galdiero MR, Marone G, Cristinziano L, Granata F, Marone G Tags: Curr Opin Immunol Source Type: research

Strategies for a multi-stage neutralizing antibody-based HIV vaccine.
Abstract A critical property of a prophylactic HIV vaccine is likely to be its ability to elicit broadly neutralizing antibodies (bnAbs). BnAbs typically have multiple unusual features and are generated in a fraction of HIV-infected individuals through complex pathways. Current vaccine design approaches seek to trigger rare B cell precursors and then steer affinity maturation toward bnAbs in a multi-stage multi-component immunization approach. These vaccine design strategies have been facilitated by molecular descriptions of bnAb interactions with stabilized HIV trimers, the use of an array of sophisticated approa...
Source: Current Opinion in Immunology - May 15, 2018 Category: Allergy & Immunology Authors: Andrabi R, Bhiman JN, Burton DR Tags: Curr Opin Immunol Source Type: research

Lymphatics in the liver.
Abstract The liver is the largest lymph producing organ. A significant increase in the number of hepatic lymphatic vessels, or lymphangiogenesis, has been reported in various liver diseases, including, but not limited to, cirrhosis, viral hepatitis and hepatocellular carcinoma. Despite its apparent relevance in healthy and diseased livers as these and other observations indicate, the hepatic lymphatic system has been poorly studied. With knowledge of the lymphatic system in other organs and tissues incorporated, this review article addresses the current knowledge of the hepatic lymphatic system and the potential r...
Source: Current Opinion in Immunology - May 14, 2018 Category: Allergy & Immunology Authors: Tanaka M, Iwakiri Y Tags: Curr Opin Immunol Source Type: research

Immunological responses to influenza vaccination: lessons for improving vaccine efficacy.
Abstract A critical factor in the maturation of influenza vaccine responses is the nearly inevitable binding of vaccine antigens by exiting anti-influenza IgGs. These antigen-IgG immune complexes direct the response to immunization by modulating cellular processes that determine antibody and T-cell repertoires: maturation of dendritic cells, processing and presentation of antigens to T cells, trafficking of antigens to the germinal center, and selection of B cells for antibody production. By focusing on the recent advances in the study of the immunomodulatory processes mediated by IgG immune complexes upon influen...
Source: Current Opinion in Immunology - May 10, 2018 Category: Allergy & Immunology Authors: Wang TT, Bournazos S, Ravetch JV Tags: Curr Opin Immunol Source Type: research

Antigen presentation unfolded: identifying convergence points between the UPR and antigen presentation pathways.
Abstract The unfolded protein response (UPR) is an adaptive response meant to restore endoplasmic reticulum homeostasis in conditions of ER stress that subvert the folding capacity of the cell. Over the past few years, it has become clear that the functions of the UPR stretch far beyond their canonical role and intersect with seemingly unrelated functions such as innate immunity and antigen presentation. The aim of the present review is to dissect how the UPR interferes directly and indirectly with the major processes of MHC-I and MHC-II antigen presentation. PMID: 29754111 [PubMed - as supplied by publisher]...
Source: Current Opinion in Immunology - May 10, 2018 Category: Allergy & Immunology Authors: Osorio F, Lambrecht BN, Janssens S Tags: Curr Opin Immunol Source Type: research

MR1 antigen presentation to MAIT cells: new ligands, diverse pathways?
Abstract The major histocompatibility complex class I-related molecule MR1 is the only antigen (Ag) presenting molecule that captures and displays vitamin B-derived metabolites that are unique to a wide array of microbes. Presentation of these metabolite Ag at the cell surface activates mucosal-associated invariant T (MAIT) cells, a highly abundant innate-like T cell population, and represents a recently-described mechanism used by the mammalian immune system to sense pathogenic or commensal microbes. Our understanding of the cell biology of how MR1 accomplishes this unique task is still evolving, but recent advan...
Source: Current Opinion in Immunology - May 10, 2018 Category: Allergy & Immunology Authors: McWilliam HE, Villadangos JA Tags: Curr Opin Immunol Source Type: research

Zika virus vaccines: immune response, current status, and future challenges.
Abstract Zika virus (ZIKV) is the most recent mosquito-transmitted virus to cause a global health crisis following its entrance into a naïve population in the Western Hemisphere. Once the ZIKV outbreak began investigators rapidly established small and large animal models of pathogenesis, developed a number candidate vaccines using different platforms, and defined mechanisms of protection. In this review, we characterize the adaptive immune response elicited by ZIKV infections and vaccines, the status of ongoing clinical trials in humans, and discuss future challenges within the field. PMID: 29753210 [Pub...
Source: Current Opinion in Immunology - May 9, 2018 Category: Allergy & Immunology Authors: Richner JM, Diamond MS Tags: Curr Opin Immunol Source Type: research

Sustainable vaccine development: a vaccine manufacturer's perspective.
Abstract Vaccination remains the most cost-effective public health intervention after clean water, and the benefits impressively outweigh the costs. The efforts needed to fulfill the steadily growing demands for next-generation and novel vaccines designed for emerging pathogens and new indications are only realizable in a sustainable business model. Vaccine development can be fast-tracked through strengthening international collaborations, and the continuous innovation of technologies to accelerate their design, development, and manufacturing. However, these processes should be supported by a balanced project port...
Source: Current Opinion in Immunology - May 8, 2018 Category: Allergy & Immunology Authors: Rappuoli R, Hanon E Tags: Curr Opin Immunol Source Type: research

From human antibody structure and function towards the design of a novel Plasmodium falciparum circumsporozoite protein malaria vaccine.
Abstract Malaria is a life-threatening vector-borne disease caused by Plasmodium parasites that infect millions of people in endemic areas every year. The most advanced malaria vaccine candidate RTS,S targets the immune response against circumsporozoite protein of Plasmodium falciparum (PfCSP), the most deadly Plasmodium species in humans. PfCSP plays a fundamental role in parasite development as well as the establishment of the infection and is a molecular target of protective antibodies. However, RTS,S shows overall low efficacy and insufficient long-term protection. Therefore, a major goal in the development of...
Source: Current Opinion in Immunology - May 8, 2018 Category: Allergy & Immunology Authors: Wardemann H, Murugan R Tags: Curr Opin Immunol Source Type: research

Influenza vaccines: 'tailor-made' or 'one fits all'.
Abstract Currently used inactivated influenza vaccines aim at the induction of virus-neutralizing antibodies directed to the variable head domain of the viral hemagglutinin. Although these vaccines are effective against antigenically matching virus strains, they offer little protection against antigenically distinct drift variants or potentially pandemic viruses of alternative subtypes. In the last decades, the threat of novel influenza pandemics has sparked research efforts to develop vaccines that induce more broadly protective immunity. Here, we discuss the immune responses induced by conventional 'tailor-made'...
Source: Current Opinion in Immunology - May 4, 2018 Category: Allergy & Immunology Authors: Saletti G, Gerlach T, Rimmelzwaan GF Tags: Curr Opin Immunol Source Type: research

Lipids hide or step aside for CD1-autoreactive T cell receptors.
Abstract Peptide and lipid antigens are presented to T cells when bound to MHC or CD1 proteins, respectively. The general paradigm of T cell antigen recognition is that T cell receptors (TCRs) co-recognize an epitope comprised of the antigen and antigen presenting molecule. Here we review the latest studies in which T cells operate outside the co-recognition paradigm: TCRs can broadly contact CD1 itself, but not the carried lipid. The essential structural feature in these new mechanisms is a large 'antigen free' zone on the outer surface of certain antigen presenting molecules. Whereas peptides dominate the expose...
Source: Current Opinion in Immunology - May 4, 2018 Category: Allergy & Immunology Authors: Cotton RN, Shahine A, Rossjohn J, Moody DB Tags: Curr Opin Immunol Source Type: research

Shaping a universally broad antibody response to influenza amidst a variable immunoglobulin landscape.
Abstract One hundred years ago, the 1918 H1N1 Pandemic killed 20 million people worldwide. Despite the introduction of a worldwide surveillance system, large-scale production of influenza vaccines coupled with annual vaccination schemes, influenza remains a major public health concern. Prevention of influenza on a population basis requires intimate knowledge of the interplay between the virus' ability to escape the immune response and persistent recall and regeneration of the antibody response. Here we will briefly outline the nature of the antibody response, focusing on the response to intransigent regions of the...
Source: Current Opinion in Immunology - May 3, 2018 Category: Allergy & Immunology Authors: Andrews SF, McDermott AB Tags: Curr Opin Immunol Source Type: research

Immune evasion of the CD1d/NKT cell axis.
Abstract Many reviews on the CD1d/NKT cell axis focus on the ability of CD1d-restricted NKT cells to serve as effector cells in a variety of disorders, be they infectious diseases, cancer or autoimmunity. In contrast, here, we discuss the ways that viruses, bacteria and tumor cells can evade the CD1d/NKT cell axis. As a result, these disease states have a better chance to establish a foothold and potentially cause problems for the subsequent adaptive immune response, as the host tries to rid itself of infections or tumors. PMID: 29734045 [PubMed - as supplied by publisher] (Source: Current Opinion in Immunology)
Source: Current Opinion in Immunology - May 3, 2018 Category: Allergy & Immunology Authors: Brutkiewicz RR, Yunes-Medina L, Liu J Tags: Curr Opin Immunol Source Type: research

Adoptive T cell therapy: points to consider.
Abstract Adoptive Cell Therapy (ACT) has enjoyed a revival in recent years with the approval of CAR T cells for the treatment of patients with B cell malignancies. Advancing the use of adoptively transferred T cells for the treatment of patients with solid tumor and other hematologic malignancies however, will require addressing numerous effector cell intrinsic as well as tumor micro environmental hurdles and exploiting a broader ACT platform that includes not only engineered CAR-T cells, but also other forms of ACT including Endogenous T Cell (ETC) and Tumor-infiltrating Lymphocyte (TIL) therapy. In this review, ...
Source: Current Opinion in Immunology - May 2, 2018 Category: Allergy & Immunology Authors: Yee C Tags: Curr Opin Immunol Source Type: research

Why do proteases mess up with antigen presentation by re-shuffling antigen sequences?
We describe in this review what we know about the immunological relevance of post-translationally spliced epitopes and why proteases seem to have a second (dark) personality, which is keen to create new peptide bonds. PMID: 29723668 [PubMed - as supplied by publisher] (Source: Current Opinion in Immunology)
Source: Current Opinion in Immunology - April 30, 2018 Category: Allergy & Immunology Authors: Liepe J, Ovaa H, Mishto M Tags: Curr Opin Immunol Source Type: research

Endocytosis regulation by autophagy proteins in MHC restricted antigen presentation.
, Münz C Abstract The macroautophagy machinery supports membrane remodeling and fusion events that lead to the engulfment of cytoplasmic constituents in autophagosomes and their degradation in lysosomes. The capacity of this machinery to regulate membrane adaptors and influence vesicle fusion with lysosomes seems to be used not only for autophagosomes, but also for endosomes. We summarize recent evidence that two aspects of endocytosis are regulated by parts of the macroautophagy machinery. These are recruitment of adaptors for the internalization of surface receptors and the fusion of phagosomes with lysosom...
Source: Current Opinion in Immunology - April 29, 2018 Category: Allergy & Immunology Authors: Keller CW, Loi M, Ligeon LA, Gannagé M, Lünemann JD, Münz C Tags: Curr Opin Immunol Source Type: research

Improving influenza vaccines: challenges to effective implementation.
Abstract Influenza virus causes contagious respiratory illness and remains a major burden on healthcare systems and the economy. Seasonal influenza vaccine is the most cost-effective way to combat the disease. However, underestimation of disease severity and controversy over vaccine safety and effectiveness hampers public confidence in vaccination. Action is needed to restore public confidence and improve vaccine uptake. Tailoring seasonal influenza vaccines according to immune responsiveness and infection/vaccination history of different populations can improve vaccine efficacy and effectiveness. Steady progress ...
Source: Current Opinion in Immunology - April 29, 2018 Category: Allergy & Immunology Authors: Zhou F, Trieu MC, Davies R, Cox RJ Tags: Curr Opin Immunol Source Type: research

Role of calcium permeable channels in dendritic cell migration.
;nil AM, Vargas P Abstract Calcium ion (Ca2+) is an essential second messenger involved in multiple cellular and subcellular processes. Ca2+ can be released and sensed globally or locally within cells, providing complex signals of variable amplitudes and time-scales. The key function of Ca2+ in the regulation of acto-myosin contractility has provided a simple explanation for its role in the regulation of immune cell migration. However, many questions remain, including the identity of the Ca2+ stores, channels and upstream signals involved in this process. Here, we focus on dendritic cells (DCs), because their immu...
Source: Current Opinion in Immunology - April 28, 2018 Category: Allergy & Immunology Authors: Sáez PJ, Sáez JC, Lennon-Duménil AM, Vargas P Tags: Curr Opin Immunol Source Type: research

Antibody-based vaccine strategies against intracellular pathogens.
Abstract Historically, antibody-mediated immunity was considered effective against toxins, extracellular pathogens and viruses, while control of intracellular pathogens was the domain of cellular immunity. However, numerous observations in recent decades have conclusively shown that antibody can protect against intracellular pathogens. This paradigmatic shift has tremendous implications for immunology and vaccine design. For immunology the observation that antibody can protect against intracellular pathogens has led to the discovery of new mechanisms of antibody action. For vaccine design the knowledge that humora...
Source: Current Opinion in Immunology - April 25, 2018 Category: Allergy & Immunology Authors: Casadevall A Tags: Curr Opin Immunol Source Type: research

Lymphatic endothelial progenitor cells: origins and roles in lymphangiogenesis.
Abstract How are lymphatic vessels built? What are the sources of progenitor cells employed to construct lymphatic vessels during embryogenesis and in pathological situations? Are lymphatic vessels in different tissues built the same way? These questions have been highly topical and actively debated in the field of lymphangiogenesis research for more than 100 years. While embryonic veins and cells of mesenchymal origin have been recognised as sources of embryonic lymphatic endothelial cells for many years, recent advances in technology have revealed the existence of additional sources of lymphatic endothelial cell...
Source: Current Opinion in Immunology - April 25, 2018 Category: Allergy & Immunology Authors: Kazenwadel J, Harvey NL Tags: Curr Opin Immunol Source Type: research

Involvement of ion channels in allergy.
Abstract Allergic asthma is a complex disease, often characterized by an inappropriate Th2 response to normally harmless allergens. Epithelial cells damaged or activated by the allergen produce IL-33, TSLP and IL-25, activating ILC2 and dendritic cells. The latter migrate into lymph nodes where they induce Th2-cell commitment. Th2 and other type 2 innate inflammatory cells trigger inflammation and airway hyper-reactivity. The toolbox consisting of the ion channels varies from one cellular type to another and depends on its activation state, offering the possibility to design novel drugs in the field of allergy. We...
Source: Current Opinion in Immunology - April 25, 2018 Category: Allergy & Immunology Authors: Pelletier L, Savignac M Tags: Curr Opin Immunol Source Type: research

The evolving role of lymphatics in cancer metastasis.
Abstract While the link between the lymphatic system and the metastatic spread of cancer is centuries old, understanding of the underlying mechanisms is still evolving. Lymphatic vessels provide a route for tumour cells to reach regional lymph nodes (LNs), which is prognostic of distant organ metastasis and poor survival. However, genomic analyses of metastatic cancer now reveal complex patterns of dissemination. The lymphatic endothelial cells lining lymphatics respond to molecular cues from the tumour microenvironment, mediating growth and remodelling of lymphatic vessels at the primary tumour, draining LNs and ...
Source: Current Opinion in Immunology - April 23, 2018 Category: Allergy & Immunology Authors: Farnsworth RH, Achen MG, Stacker SA Tags: Curr Opin Immunol Source Type: research

Development of next generation hemagglutinin-based broadly protective influenza virus vaccines.
Abstract Influenza viruses are a severe threat to human health and current vaccines do not provide sufficient protection. The highly variable nature of influenza viruses has made the production of efficacious vaccines a challenge. In recent years, a multitude of novel, broadly reactive influenza virus vaccination approaches have been described. What has long seemed impossible could now become reality in the near future-a new generation of influenza virus vaccines that provides long-lasting and broad protection against seasonal as well as potentially pandemic influenza virus strains. This review will discuss new he...
Source: Current Opinion in Immunology - April 19, 2018 Category: Allergy & Immunology Authors: Nachbagauer R, Palese P Tags: Curr Opin Immunol Source Type: research

Cytokines regulating lymphangiogenesis.
lsh L Abstract Lymphatic vessels are established by differentiation of lymphendothelial progenitors during embryogenesis. Lymphangiogenesis, the formation of new lymphatic vessels from pre-existing ones is rare in the healthy adult but takes place during pathological conditions such as inflammation, tissue repair and tumor growth. Conditions of dysfunctional lymphatics exist after surgical interventions or in certain genetic diseases. A key lymphangiogenic stimulator is vascular endothelial growth factor-C (VEGFC) acting on VEGF receptor-3 (VEGFR3) expressed on lymphendothelial cells. Other cytokines may act direc...
Source: Current Opinion in Immunology - April 19, 2018 Category: Allergy & Immunology Authors: Sáinz-Jaspeado M, Claesson-Welsh L Tags: Curr Opin Immunol Source Type: research

Universal influenza virus vaccines and therapeutics: where do we stand with influenza B virus?
Abstract The development of a broadly protective or universal influenza virus vaccine is currently a public health priority worldwide. The vast majority of these efforts is exclusively focused on influenza A viruses. While influenza A viruses cause the majority of all influenza cases worldwide, influenza B viruses should not be ignored. Approximately 25% of all influenza cases are caused by influenza B viruses which circulate as two distinct B/Victoria/2/87-like and B/Yamagata/16/88-like lineages. In contrast to popular belief, influenza B cases frequently cause significant morbidity and mortality, especially in c...
Source: Current Opinion in Immunology - April 17, 2018 Category: Allergy & Immunology Authors: Tan J, Asthagiri Arunkumar G, Krammer F Tags: Curr Opin Immunol Source Type: research

Neuraminidase as an influenza vaccine antigen: a low hanging fruit, ready for picking to improve vaccine effectiveness.
Abstract Neuraminidase (NA) plays an essential role in influenza virus replication, facilitating multicycle infection predominantly by releasing virions from infected cells. NA-inhibiting antibodies provide resistance to disease and NA-specific antibodies contribute to vaccine efficacy. The primary reason NA vaccine content and immunogenicity was not routinely measured in the past, was the lack of suitable assays to quantify NA and NA-specific antibodies. These are now available and with recent appreciation of its contribution to immunity, NA content of seasonal and pandemic vaccines is being considered. An added ...
Source: Current Opinion in Immunology - April 16, 2018 Category: Allergy & Immunology Authors: Eichelberger MC, Morens DM, Taubenberger JK Tags: Curr Opin Immunol Source Type: research

Updates on antibody functions in Mycobacterium tuberculosis infection and their relevance for developing a vaccine against tuberculosis.
Abstract A more effective vaccine to control tuberculosis (TB), a major global public health problem, is urgently needed. Current vaccine candidates focus predominantly on eliciting cell-mediated immunity but other arms of the immune system also contribute to protection against TB. We review here recent studies that enhance our current knowledge of antibody-mediated functions against Mycobacterium tuberculosis. These findings, which contribute to the increasing evidence that antibodies have a protective role against TB, include demonstrations that firstly distinct human antibody Fc glycosylation patterns, found in...
Source: Current Opinion in Immunology - April 12, 2018 Category: Allergy & Immunology Authors: Achkar JM, Prados-Rosales R Tags: Curr Opin Immunol Source Type: research

Obesity induced T cell dysfunction and implications for cancer immunotherapy.
Abstract Obesity has been shown to increase risk for a number of different disorders, including cancer. In addition, obesity is also associated with immune dysfunction, which could contribute to its strong association with other comorbidities. Recently, the immune system has been found to be heavily regulated by changes in metabolism. In particular, T cells are able to respond to intrinsic metabolic regulatory mechanisms, as well as extrinsic factors such as the changes in metabolite availability. The dysfunctional metabolic environment created by obesity could therefore have a direct impact on T cell responses. I...
Source: Current Opinion in Immunology - April 11, 2018 Category: Allergy & Immunology Authors: Aguilar EG, Murphy WJ Tags: Curr Opin Immunol Source Type: research

Mass cytometry: a powerful tool for dissecting the immune landscape.
Abstract Advancement in methodologies for single cell analysis has historically been a major driver of progress in immunology. Currently, high dimensional flow cytometry, mass cytometry and various forms of single cell sequencing-based analysis methods are being widely adopted to expose the staggering heterogeneity of immune cells in many contexts. Here, we focus on mass cytometry, a form of flow cytometry that allows for simultaneous interrogation of more than 40 different marker molecules, including cytokines and transcription factors, without the need for spectral compensation. We argue that mass cytometry occu...
Source: Current Opinion in Immunology - April 11, 2018 Category: Allergy & Immunology Authors: Simoni Y, Chng MHY, Li S, Fehlings M, Newell EW Tags: Curr Opin Immunol Source Type: research

Natural killer cells target and differentiate cancer stem-like cells/undifferentiated tumors: strategies to optimize their growth and expansion for effective cancer immunotherapy.
Abstract Natural killer (NK) cells are known to select and differentiate cancer stem-like cells/undifferentiated tumors via lysis, and secreted/membrane bound IFN-γ and TNF-α respectively, resulting in the control of tumor growth. Several in vivo mouse models including humanized-BLT mice have been used to study the biology and significance of NK cells in selection/differentiation of stem-like tumors within the context of a reconstituted human immune system. In addition, we discuss the evidence and significance of NK cell loss at the pre-neoplastic stage. Therefore, because of their indispensable role i...
Source: Current Opinion in Immunology - April 10, 2018 Category: Allergy & Immunology Authors: Kaur K, Nanut MP, Ko MW, Safaie T, Kos J, Jewett A Tags: Curr Opin Immunol Source Type: research

Ion channelopathies of the immune system.
Abstract Ion channels and transporters move ions across membrane barriers and are essential for a host of cell functions in many organs. They conduct K+, Na+ and Cl-, which are essential for regulating the membrane potential, H+ to control intracellular and extracellular pH and divalent cations such as Ca2+, Mg2+ and Zn2+, which function as second messengers and cofactors for many proteins. Inherited channelopathies due to mutations in ion channels or their accessory proteins cause a variety of diseases in the nervous, cardiovascular and other tissues, but channelopathies that affect immune function are not as wel...
Source: Current Opinion in Immunology - April 7, 2018 Category: Allergy & Immunology Authors: Vaeth M, Feske S Tags: Curr Opin Immunol Source Type: research

Modulation of innate and adaptive immunity by P2X ion channels.
Abstract Extracellular ATP is a major component of the inflammatory microenvironment where it accumulates following cell and tissue injury but also as a consequence of non-lytic release from activated inflammatory cells. In the inflammatory microenvironment ATP binds and activates nucleotide receptors of the P2Y and P2X subfamilies expressed by immune cells. P2Y receptors are G-protein-coupled, while P2X receptors are cation-selective channels. Changes in the intracellular ion homeostasis triggered by P2X receptor stimulation trigger multiple key responses crucial for initiation, propagation, and resolution of inf...
Source: Current Opinion in Immunology - April 6, 2018 Category: Allergy & Immunology Authors: Di Virgilio F, Sarti AC, Grassi F Tags: Curr Opin Immunol Source Type: research

Vaccine options for influenza: thinking small.
Abstract Vaccines that direct the immune response towards conserved B cell epitopes of influenza viruses can provide broad protection. In many instances, this requires the design of vaccine antigens that stimulate the immune system to levels that far exceed the natural responses towards such antigens. Here we focus on the matrix protein 2 ectodomain (M2e) as a 'universal' influenza A vaccine candidate. Thanks to its small size and high solubility, M2e can be expressed and delivered in almost any format. Protection against experimental influenza A virus challenge by M2e-based vaccines has been demonstrated in natur...
Source: Current Opinion in Immunology - April 6, 2018 Category: Allergy & Immunology Authors: Schepens B, De Vlieger D, Saelens X Tags: Curr Opin Immunol Source Type: research

Distinct and complementary roles of CD4 T cells in protective immunity to influenza virus.
Abstract CD4 T cells play a multiplicity of roles in protective immunity to influenza. Included in these functions are help for high affinity antibody production, enhancement of CD8 T cell expansion, function and memory, acceleration of the early innate response to infection and direct cytotoxicity. The influenza-specific CD4 T cell repertoire in humans established through exposures to infection and vaccination has been found to be highly variable in abundance, specificity and functionality. Deficits in particular subsets of CD4 T cells recruited into the response result in diminished antibody responses and protec...
Source: Current Opinion in Immunology - April 2, 2018 Category: Allergy & Immunology Authors: Sant AJ, Richards KA, Nayak J Tags: Curr Opin Immunol Source Type: research

Transcriptional programming of tissue-resident memory CD8+ T cells.
Abstract Tissue-resident memory CD8+ T cells (TRM) are localized in non-lymphoid tissues throughout the body where they mediate long-lived protective immunity at common sites of pathogen exposure. As the signals controlling TRM differentiation are uncovered, it is becoming apparent that the dynamic activities of numerous transcription factors are intricately involved in TRM formation. Here, we highlight known transcriptional regulators of TRM differentiation and discuss how understanding the transcriptional programming of CD8+ T cell residency in non-lymphoid tissues can be leveraged to prevent or treat disease. ...
Source: Current Opinion in Immunology - April 2, 2018 Category: Allergy & Immunology Authors: Milner JJ, Goldrath AW Tags: Curr Opin Immunol Source Type: research

Plasticity and biological diversity of myeloid derived suppressor cells.
Abstract Myeloid derived suppressor cells (MDSCs) are immature myeloid cells characterized by diverse phenotypes and functions. They impair effector functions of immune cells and promote tumor growth, angiogenesis, and tissue damage. In pathologies characterized by chronic inflammation, MDSCs are arrested in their immature state and migrate from the bone marrow to the periphery and to the site of inflammation, where they mediate immunosuppression. When reaching new environments, which exhibit a different array of cytokines, chemokines, and pro-inflammatory mediators, MDSCs sense and adapt to the altered micro-envi...
Source: Current Opinion in Immunology - March 31, 2018 Category: Allergy & Immunology Authors: Ben-Meir K, Twaik N, Baniyash M Tags: Curr Opin Immunol Source Type: research

Multiple roles of lymphatic vessels in tumor progression.
Abstract Sentinel lymph node metastasis is a prognostic indicator for systemic tumor spread in many types of cancers, and tumor lymphangiogenesis correlates with reduced survival. Consequently, lymphatic vessels have been suggested to promote tumor progression in multiple ways. Tumor lymphangiogenesis occurs both in primary tumors and at distant (pre-) metastatic sites, and facilitates lymphatic invasion and tumor cell dissemination. Lymphatic vessels have also emerged as regulators of tumor immunity, transporting tumor antigens to lymph nodes and directly interacting with immune cells. Furthermore, lymphatic vess...
Source: Current Opinion in Immunology - March 29, 2018 Category: Allergy & Immunology Authors: Ma Q, Dieterich LC, Detmar M Tags: Curr Opin Immunol Source Type: research

Next generation natural killer cells for cancer immunotherapy: the promise of genetic engineering.
Abstract Recent advances in the field of cellular therapy have focused on autologous T cells engineered to express a chimeric antigen receptor (CAR) against tumor antigens. Remarkable responses have been observed in patients receiving autologous CD19-redirected T cells for the treatment of B-lymphoid malignancies. However, the generation of autologous products for each patient is logistically challenging and expensive. Extensive research efforts are ongoing to generate an off-the-shelf cellular product for the treatment of cancer patients. Natural killer (NK) cells are attractive contenders since they have potent ...
Source: Current Opinion in Immunology - March 29, 2018 Category: Allergy & Immunology Authors: Daher M, Rezvani K Tags: Curr Opin Immunol Source Type: research

Toward universal influenza virus vaccines: from natural infection to vaccination strategy.
Abstract Conceptually, a universal influenza vaccine should elicit broadly protective antibody responses targeting highly conserved epitope(s) shared by various virus strains. Strategically directing antibody immunity to the conserved hemagglutinin stalk has recently emerged as a promising approach that is substantiated by the identification of naturally occurring, stalk-reactive human antibodies capable of conferring broad protection against influenza virus challenge in animal models. Despite all the advancements, future realization of this strategy still faces many challenges, particularly whether it is able to ...
Source: Current Opinion in Immunology - March 28, 2018 Category: Allergy & Immunology Authors: Zhao C, Xu J Tags: Curr Opin Immunol Source Type: research

The purinergic P2X7 ion channel receptor-a 'repair' receptor in bone.
en NR Abstract A strong skeleton relies on adaptation to varying physical demands and on maintenance of the bone tissue in order to avoid accumulation of micro-damage. In bone, the purinergic P2X7 ion channel receptor is expressed on both cells of the stromal lineage such as the bone forming osteoblasts and the mechano-sensing osteocytes and on cells belonging to the immune-related monocyte-macrophage lineage, the bone resorbing osteoclasts. Recent studies have demonstrated that the receptor plays important roles in the anabolic responses to mechanical loading on bone and, together with the pannexin1 hemi-channel,...
Source: Current Opinion in Immunology - March 24, 2018 Category: Allergy & Immunology Authors: Jørgensen NR Tags: Curr Opin Immunol Source Type: research

Engineering T cells for adoptive therapy: outsmarting the tumor.
Abstract Adoptive transfer of T cells gene-engineered with antigen-specific receptors, whether it be chimeric antigen receptors (CARs) or T cell receptors (TCRs), has proven its feasibility and therapeutic potential in the treatment of tumors. Despite clinical successes, the majority of patients experiences no or non-sustainable clearance of solid tumors, which is attributed to local T cell evasive mechanisms. A rapidly expanding understanding of molecular and cellular events that contribute to a reduction in numbers and/or activation of intra-tumor T cells has facilitated the development of gene-engineering strat...
Source: Current Opinion in Immunology - March 23, 2018 Category: Allergy & Immunology Authors: Kunert A, Debets R Tags: Curr Opin Immunol Source Type: research

Chemokines and cancer: new immune checkpoints for cancer therapy.
Abstract The current review focuses on two chemokine-chemokine receptor interactions: CXCL10-CXCR3 and CCL1-CCR8. We show that CXCL10 acts on CD4+ and CD8+ T cells to enhance anti-tumor immunity, and explore the translational perspectives of these findings. As for CCR8 very recently, we identified a novel subset of CCR8+CD4+FOXp3+ regulatory T cells (Treg) that are major drivers of immune regulation. We observed that one of the four CCR8 ligands, CCL1, produced by these cells, potentiates their suppressive activity via induction of CCR8, FOXp3, CD39, Granzyme-B, and IL-10 in a positive feedback mechanism, making t...
Source: Current Opinion in Immunology - March 23, 2018 Category: Allergy & Immunology Authors: Karin N Tags: Curr Opin Immunol Source Type: research

Modulating ion channel function with antibodies and nanobodies.
Abstract Immune cells express various voltage-gated and ligand-gated ion channels that mediate the influx and efflux of charged ions across the plasma membrane, thereby controlling the membrane potential and mediating intracellular signal transduction pathways. These channels thus present potential targets for experimental modulation of immune responses and for therapeutic interventions in immune disease. Small molecule drugs and natural toxins acting on ion channels have illustrated the potential therapeutic benefit of targeting ion channels on immune cells. Unwanted side effects and immunogenicity have however h...
Source: Current Opinion in Immunology - March 23, 2018 Category: Allergy & Immunology Authors: Stortelers C, Pinto-Espinoza C, Van Hoorick D, Koch-Nolte F Tags: Curr Opin Immunol Source Type: research

Regulation of human dendritic cell immune functions by ion channels.
Abstract Dendritic cells (DCs) are highly specialized antigen-presenting cells (APCs) able to induce both specific immunity and immune tolerance. Using information gathered from the tissue where they reside, DCs adjust their functional activity to ensure that protective immunity is favoured while unwanted or exaggerated immune responses are prevented. The remarkable ability of these cells to induce, enhance and orient the immune response, while at the same time maintaining self-tolerance, makes them key players in the immune system. Despite the fact that the role of Ca2+ has been clearly established in human DC fu...
Source: Current Opinion in Immunology - March 22, 2018 Category: Allergy & Immunology Authors: Vandier C, Velge-Roussel F Tags: Curr Opin Immunol Source Type: research

The transition from HLA-I positive to HLA-I negative primary tumors: the road to escape from T-cell responses.
Abstract MHC/HLA class I loss in cancer is one of the main mechanisms of tumor immune escape from T-cell recognition and destruction. Tumor infiltration by T lymphocytes (TILs) and by other immune cells was first described many years ago, but has never been directly and clearly linked to the destruction of HLA-I positive and selection of HLA-I negative tumor cells. The degree and the pattern of lymphocyte infiltration in a tumor nest may depend on antigenicity and the developmental stages of the tumors. In addition, it is becoming evident that HLA-I expression and tumor infiltration have a direct correlation with ...
Source: Current Opinion in Immunology - March 19, 2018 Category: Allergy & Immunology Authors: Aptsiauri N, Ruiz-Cabello F, Garrido F Tags: Curr Opin Immunol Source Type: research