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Trends in Immunology

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https://www.readbyqxmd.com/read/28089218/nkg2d-signaling-the-immune-subversive-side-of-hdac3
#1
Alicia R Folgueras, Segundo Gonzalez, Alejandro López-Soto
Natural killer (NK) cells are alerted to infected and transformed cells by local upregulation of ligands for the NK-activating receptor NKG2D. In a recent report, Greene et al. unveil a new mechanism that induces the expression of the NKG2D ligand retinoic acid early-inducible (RAE-1) in response to murine cytomegalovirus (MCMV) infection through inhibition of casein kinase 2 (CK2), an activator of the repressor histone deacetylase HDAC3.
January 11, 2017: Trends in Immunology
https://www.readbyqxmd.com/read/28082101/negative-regulation-of-type-2-immunity
#2
REVIEW
Dimitri A de Kouchkovsky, Sourav Ghosh, Carla V Rothlin
Type 2 immunity encompasses the mechanisms through which the immune system responds to helminths and an array of environmental substances such as allergens. In the developing world, billions of individuals are chronically infected with endemic parasitic helminths. In comparison, in the industrialized world, millions of individuals suffer from dysregulated type 2 immunity, referred to clinically as atopic diseases including asthma, allergic rhinitis, and atopic dermatitis. Thus, type 2 immunity must be carefully regulated to mount protective host responses yet avoid inappropriate activation and immunopathology...
January 9, 2017: Trends in Immunology
https://www.readbyqxmd.com/read/28073694/hiv-latency-should-we-shock-or-lock
#3
REVIEW
Gilles Darcis, Benoit Van Driessche, Carine Van Lint
Combinatory antiretroviral therapy (cART) increases the survival and quality of life of HIV-1-infected patients. However, interruption of therapy almost invariably leads to the re-emergence of detectable viral replication because HIV-1 persists in viral latent reservoirs. Improved understanding of the molecular mechanisms involved in HIV-1 latency has paved the way for innovative strategies that attempt to purge latent virus. In this article we discuss the results of the broadly explored 'shock and kill' strategy, and also highlight the major hurdles facing this approach...
January 7, 2017: Trends in Immunology
https://www.readbyqxmd.com/read/28073693/crosstalk-between-cytoplasmic-rig-i-and-sting-sensing-pathways
#4
REVIEW
Alessandra Zevini, David Olagnier, John Hiscott
Detection of evolutionarily conserved molecules on microbial pathogens by host immune sensors represents the initial trigger of the immune response against infection. Cytosolic receptors sense viral and intracellular bacterial genomes, as well as nucleic acids produced during replication. Once activated, these sensors trigger multiple signaling cascades, converging on the production of type I interferons and proinflammatory cytokines. Although distinct classes of receptors are responsible for the RNA and DNA sensing, the downstream signaling components are physically and functionally interconnected...
January 7, 2017: Trends in Immunology
https://www.readbyqxmd.com/read/28017520/microbial-dysbiosis-in-common-variable-immune-deficiencies-evidence-causes-and-consequences
#5
REVIEW
Roos-Marijn Berbers, Stefan Nierkens, Jacob M van Laar, Debby Bogaert, Helen L Leavis
Common variable immunodeficiency (CVID) is an immune disorder that not only causes increased susceptibility to infection, but also to inflammatory complications such as autoimmunity, lymphoid proliferation, malignancy, and granulomatous disease. Recent findings implicate the microbiome as a driver of this systemic immune dysregulation. Here, we critically review the current evidence for a role of the microbiome in the pathogenesis of CVID immune dysregulation, and describe the possible immunologic mechanisms behind causes and consequences of microbial dysbiosis in CVID...
December 22, 2016: Trends in Immunology
https://www.readbyqxmd.com/read/27986392/solving-immunology
#6
REVIEW
Yoram Vodovotz, Ashley Xia, Elizabeth L Read, Josep Bassaganya-Riera, David A Hafler, Eduardo Sontag, Jin Wang, John S Tsang, Judy D Day, Steven H Kleinstein, Atul J Butte, Matthew C Altman, Ross Hammond, Stuart C Sealfon
Emergent responses of the immune system result from the integration of molecular and cellular networks over time and across multiple organs. High-content and high-throughput analysis technologies, concomitantly with data-driven and mechanistic modeling, hold promise for the systematic interrogation of these complex pathways. However, connecting genetic variation and molecular mechanisms to individual phenotypes and health outcomes has proven elusive. Gaps remain in data, and disagreements persist about the value of mechanistic modeling for immunology...
December 13, 2016: Trends in Immunology
https://www.readbyqxmd.com/read/27939451/transcriptional-regulation-of-tissue-resident-lymphocytes
#7
REVIEW
Laura K Mackay, Axel Kallies
Numerous innate and adaptive immune cells reside in non-lymphoid tissues, where they contribute to barrier immunity, tissue homeostasis, and immune regulation. These tissue-resident populations do not recirculate in the blood or lymphatics and adopt a unique phenotype that is distinct from immune cells in the circulation. Tissue residency has been predominantly described for memory CD8(+) T cells [tissue-resident memory T cells (TRM)], but it is now clear that CD4 T cells, regulatory T (Treg) cells, various innate T cells, and innate lymphoid cells (ILCs) can establish residence in non-lymphoid tissues...
December 8, 2016: Trends in Immunology
https://www.readbyqxmd.com/read/27964820/t-cell-exhaustion-in-glioblastoma-intricacies-of-immune-checkpoints
#8
REVIEW
Reza Mirzaei, Susobhan Sarkar, V Wee Yong
Glioblastoma is an aggressive and incurable primary brain tumor. While the blockade of immune checkpoints leads to reversal of T cell exhaustion in many cancers, the efficacy of this therapy in glioblastoma requires further consideration of the brain microenvironment beyond T cell activity. Neural cells are crucially dependent on glucose for survival, and tumor cells rabidly consume glucose; the glucose-deprived microenvironment further elevates immune checkpoint molecules to benefit tumor growth and exacerbate T cell exhaustion...
December 7, 2016: Trends in Immunology
https://www.readbyqxmd.com/read/27919707/autoimmune-cardiotoxicity-of-cancer-immunotherapy
#9
Feixiong Cheng, Joseph Loscalzo
Contemporary immunotherapies (e.g., immune checkpoint inhibitors), which enhance the immune response to cancer cells, improve clinical outcomes in several malignancies. A recent study reported the cases of two patients with metastatic melanoma who developed fatal myocarditis during ipilimumab and nivolumab combination immunotherapy; these examples highlight the risk of unbridled activation of the immune system.
December 2, 2016: Trends in Immunology
https://www.readbyqxmd.com/read/27887993/isg15-in-sickness-and-in-health
#10
REVIEW
Mark Hermann, Dusan Bogunovic
ISG15 is a type I interferon (IFN)-inducible gene encoding a protein with pleiotropic functions, acting both as a soluble molecule and as a protein modifier. Surprisingly, and despite the antiviral functions of ISG15 described in mice, humans born with inactivating mutations of ISG15 do not present with any overt viral phenotype, but are highly susceptible to environmental mycobacteria and have autoinflammatory disease presentations. In vitro, ISG15 deficiency also leads to persistently high levels of type I IFN-stimulated gene expression and to increased resistance to all viruses tested to date...
November 22, 2016: Trends in Immunology
https://www.readbyqxmd.com/read/27842955/t-cell-development-by-the-numbers
#11
REVIEW
Andreas Krueger, Natalia Ziętara, Marcin Łyszkiewicz
T cells are continually generated in the thymus in a highly dynamic process comprising discrete steps of lineage commitment, T cell receptor (TCR) gene rearrangement, and selection. These steps are linked to distinct rates of proliferation, survival, and cell death, but a quantitative picture of T cell development is only beginning to emerge. Here we summarize recent technical advances, including genetic fate mapping, barcoding, and molecular timers, that have allowed the implementation of computational models to quantify developmental dynamics in the thymus...
November 11, 2016: Trends in Immunology
https://www.readbyqxmd.com/read/27939452/mhc-bias-by-t-cell-receptors-genetic-evidence-for-mhc-and-tcr-coevolution
#12
Brian M Baker, Brian D Evavold
Major histocompatibility complex (MHC) restriction is a fundamental tenet of T cell biology, but the underlying mechanisms have remained controversial. The extent to which T cell receptors (TCRs) are biased towards MHC proteins in particular has been widely discussed. In a recent paper, Sharon et al. report direct evidence for coevolution between TCR and MHC genes, helping to explain how MHC compatibility and bias can be encoded within TCRs.
January 2017: Trends in Immunology
https://www.readbyqxmd.com/read/27916385/noncanonical-antiviral-mechanisms-of-isgs-dispensability-of-inducible-interferons
#13
LETTER
Lei Xu, Wenshi Wang, Maikel P Peppelenbosch, Qiuwei Pan
No abstract text is available yet for this article.
January 2017: Trends in Immunology
https://www.readbyqxmd.com/read/27889398/recognition-of-mycobacterial-lipids-by-immune-receptors
#14
REVIEW
Eri Ishikawa, Daiki Mori, Sho Yamasaki
Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), infects one-third of the world's population and causes 1.5 million deaths each year. The cell envelopes of mycobacteria comprise a wealth of unique glycolipids, including trehalose-6,6'-dimycolate (TDM), lipoarabinomannan (LAM), lipomannan (LM), and phosphatidylinositol (PI) mannosides (PIMs). These lipids are important modulators of the host immune responses during infection and in some cases have been used as adjuvants [e.g., complete Freund's adjuvant (CFA)]...
January 2017: Trends in Immunology
https://www.readbyqxmd.com/read/27863906/post-translational-control-of-intracellular-pathogen-sensing-pathways
#15
REVIEW
Cindy Chiang, Michaela U Gack
Mammalian cells recognize virus-derived nucleic acids using a defined set of intracellular sensors including the DNA sensors cyclic GMP-AMP (cGAMP) synthase (cGAS) and interferon gamma (IFNγ)-inducible protein 16 (IFI16) as well as viral RNA receptors of the retinoic acid-inducible gene I (RIG-I)-like receptor (RLR) family. Following innate immune recognition, these sensors launch an immune response that is characterized by the transcriptional upregulation of many antiviral molecules, including proinflammatory cytokines, chemokines, and IFN-stimulated genes...
January 2017: Trends in Immunology
https://www.readbyqxmd.com/read/27856145/sequence-specific-sensing-of-nucleic-acids
#16
REVIEW
Nicolas Vabret, Nina Bhardwaj, Benjamin D Greenbaum
Innate immune cells are endowed with many nucleic acid receptors, but the role of sequence in the detection of foreign organisms remains unclear. Can sequence patterns influence recognition? In addition, how can we infer those patterns from sequence data? Here, we detail recent computational and experimental evidence associated with sequence-specific sensing. We review the mechanisms underlying the detection and discrimination of foreign sequences from self. We also describe quantitative approaches used to infer the stimulatory capacity of a given pathogen nucleic acid species, and the influence of sequence-specific sensing on host-pathogen coevolution, including endogenous sequences of foreign origin...
January 2017: Trends in Immunology
https://www.readbyqxmd.com/read/27810463/friend-or-foe-the-ambiguous-role-of-innate-lymphoid-cells-in-cancer-development
#17
REVIEW
Jochen Mattner, Stefan Wirtz
The development of immunotherapies represents a major advance towards the effective eradication of malignant tumors. So far, therapeutic approaches have largely focused on T lymphocytes, but the innate arm of the immune system might be similarly important. Innate lymphoid cells (ILCs) are rapidly-responding cells that are functionally analogous to diverse T cell subsets. In recent years these cells have attracted enormous attention owing to their pleiotropic effects in early host defense to infection and organ pathologies...
January 2017: Trends in Immunology
https://www.readbyqxmd.com/read/27793572/tigit-a-key-inhibitor-of-the-cancer-immunity-cycle
#18
REVIEW
Nicholas A Manieri, Eugene Y Chiang, Jane L Grogan
Immunotherapies that harness the activity of the immune system against tumors are proving to be an effective therapeutic approach in multiple malignancies. Indeed, through accumulation of genetic mutations, many tumors express antigens that can potentially elicit specific tumor immunity. However, tumors can also suppress these responses by activating negative regulatory pathways and checkpoints such as PD-1/PD-L1 and CTLA-4. Blocking these checkpoints on T cells has provided dramatic clinical benefit, but only a subset of patients exhibit clear and durable responses, suggesting that other mechanisms must be limiting the immune response...
January 2017: Trends in Immunology
https://www.readbyqxmd.com/read/27793571/nociceptor-sensory-neuron-immune-interactions-in-pain-and-inflammation
#19
REVIEW
Felipe A Pinho-Ribeiro, Waldiceu A Verri, Isaac M Chiu
Nociceptor sensory neurons protect organisms from danger by eliciting pain and driving avoidance. Pain also accompanies many types of inflammation and injury. It is increasingly clear that active crosstalk occurs between nociceptor neurons and the immune system to regulate pain, host defense, and inflammatory diseases. Immune cells at peripheral nerve terminals and within the spinal cord release mediators that modulate mechanical and thermal sensitivity. In turn, nociceptor neurons release neuropeptides and neurotransmitters from nerve terminals that regulate vascular, innate, and adaptive immune cell responses...
January 2017: Trends in Immunology
https://www.readbyqxmd.com/read/27838188/breaking-the-mold-partnering-with-the-national-institutes-of-health-intramural-research-program-to-accelerate-phd-training
#20
Katie Soucy, Rick M Fairhurst, Geoffrey M Lynn, Kevin Fomalont, Thomas A Wynn, Richard M Siegel
Immunology is an increasingly interdisciplinary field. Here we describe a new model for interinstitutional graduate training as partnerships between complementary laboratories. This collaborative model reduces time to graduation without compromising productivity or alumni outcomes. We offer our experience with one such program and thoughts on the ingredients for their success. Despite tremendous recent advances in technology, communications, and the translation of basic scientific discoveries into new diagnostics and therapies for human diseases, graduate training in immunology and other areas of biomedical research in the United States has remained remarkably unchanged since the early 20th century, with coursework and laboratory rotations taking up much of the first 2 years, and a single mentor shepherding the student through a research project over 3 or more subsequent years...
December 2016: Trends in Immunology
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