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Trends in Immunology

David A Rhodes, David A Isenberg
Therapeutic antibodies targeting disease-associated antigens are key tools in the treatment of cancer and autoimmunity. So far, therapeutic antibodies have targeted antigens that are, or are presumed to be, extracellular. A largely overlooked property of antibodies is their functional activity inside cells. The diverse literature dealing with intracellular antibodies emerged historically from studies of the properties of some autoantibodies. The identification of tripartite motif (TRIM) 21 as an intracellular Fc receptor linking cytosolic antibody recognition to the ubiquitin proteasome system brings this research into sharper focus...
August 11, 2017: Trends in Immunology
Anuradha Ray, Jay K Kolls
Asthma is a chronic inflammatory disorder of the airways. While the local infiltration of eosinophils and mast cells, and their role in the disease have long been recognized, neutrophil infiltration has also been assessed in many clinical studies. In these studies, airway neutrophilia was associated with asthma severity. Importantly, neutrophilia also correlates with asthma that is refractory to corticosteroids, the mainstay of asthma treatment. However, it is now increasingly recognized that neutrophils are a heterogeneous population, and a more precise phenotyping of these cells may help delineate different subtypes of asthma...
August 4, 2017: Trends in Immunology
Brian A Kidd
Technical advances in single-cell sequencing data and their application to greater samples is revealing substantial cell-to-cell variation in expression levels and propagation of this variation between molecules across cells. New quantitative approaches that apply mechanistic and statistical models in a systems-wide approach are illuminating the drivers of phenotypic diversity.
July 31, 2017: Trends in Immunology
Darienne R Myers, Julie Zikherman, Jeroen P Roose
Since the 1990s it has been known that B and T lymphocytes exhibit low-level, constitutive signaling in the basal state (tonic signaling). These lymphocytes display a range of affinity for self, which in turn generates a range of tonic signaling. Surprisingly, what signaling pathways are active in the basal state and the functional relevance of the observed tonic signaling heterogeneity remain open questions today. Here we summarize what is known about the mechanistic and functional details of tonic signaling...
July 25, 2017: Trends in Immunology
Sebastian Montealegre, Peter van Endert
Efficient (cross-)presentation of antigens internalized by dendritic cells (DCs) requires vesicular communication between the early secretory and the endocytic/phagocytic pathways, in which the Sec22b protein has been suggested to have a key role. Here, we undertake a critical assessment of two new studies that evaluate the role of Sec22b using gene-targeted mice and come to contradictory conclusions.
July 22, 2017: Trends in Immunology
Joseph P Kolb, Thomas H Oguin, Andrew Oberst, Jennifer Martinez
The life of an organism requires the assistance of an unlikely process: programmed cell death. Both development and the maintenance of homeostasis result in the production of superfluous cells that must eventually be disposed of. Furthermore, programmed cell death can also represent a defense mechanism; for example, by depriving pathogens of a replication niche. The responsibility of handling these dead cells falls on phagocytes of the immune system, which surveil their surroundings for dying or dead cells and efficiently clear them in a quiescent manner...
July 19, 2017: Trends in Immunology
Thomas Doebel, Benjamin Voisin, Keisuke Nagao
Our assumptions on the identity and functions of Langerhans cells (LCs) of the epidermis have undergone considerable changes. Once thought to be prototypic representatives of the dendritic cell (DC) lineage, they are now considered to be a specialized subset of tissue-resident macrophages. Despite this, LCs display a remarkable mixture of properties. Like many tissue macrophages, they self-maintain locally. However, unlike tissue macrophages and similar to DCs, they homeostatically migrate to lymph nodes and present antigen to antigen-specific T cells...
July 15, 2017: Trends in Immunology
Guranda Chitadze, Hans-Heinrich Oberg, Daniela Wesch, Dieter Kabelitz
γδ T cells play a role in immune surveillance because they recognize stress-induced surface molecules and metabolic intermediates that are frequently dysregulated in transformed cells. Hence, γδ T cells have attracted much interest as effector cells in cell-based immunotherapy. Recently, however, it has been realized that γδ T cells can also promote tumorigenesis through various mechanisms including regulatory activity and IL-17 production. In this review we outline both the pathways involved in cancer cell recognition and killing by γδ T cells as well as current evidence for their protumorigenic activity in various models...
July 11, 2017: Trends in Immunology
Seeyoung Choi, Richard Cornall, Renaud Lesourne, Paul E Love
THEMIS, a recently identified T-lineage-restricted protein, is the founding member of a large metazoan protein family. Gene inactivation studies have revealed a critical requirement for THEMIS during thymocyte positive selection, implicating THEMIS in signaling downstream of the T cell antigen receptor (TCR), but the mechanistic underpinnings of THEMIS function have remained elusive. A previous model posited that THEMIS prevents thymocytes from inappropriately crossing the positive/negative selection threshold by dampening TCR signaling...
July 8, 2017: Trends in Immunology
Hamish E G McWilliam, Jose A Villadangos
Mucosal-associated invariant T (MAIT) cells are innate-like lymphocytes restricted by the antigen (Ag)-presenting molecule MHC class I (MHC I)-related protein 1 (MR1). The Ags presented by MR1 are vitamin B-related Ags (VitBAgs), 'building-block' metabolites of riboflavin that are synthesized by a range of microbes. MR1 presentation is thus a unique mechanism for the immune detection of a pathogen metabolic signature. While the full picture of how MR1 accomplishes this remains incomplete, recent data show that, unlike other MHC molecules, MR1 operates by a presentation-on-demand mechanism...
July 5, 2017: Trends in Immunology
Ivaylo I Ivanov
Studying the interactions between commensal microbes and host intestinal tissue networks is challenging due to the complexity and inaccessibility of the system. A recent study reports a novel organ culture system that will enhance our ability to dissect these interactions.
July 3, 2017: Trends in Immunology
Thomas Simon, Jonathan S Bromberg
Laminins are trimeric proteins that are major components of the basement membranes that separate endothelia and epithelia from the underlying tissue. Sixteen laminin isoforms have been described, each with distinct tissue expression patterns and functions. While laminins have a critical structural role, recent evidence also indicates that they also impact the migration and functions of immune cells. Laminins are differentially expressed upon immunity or tolerance and orientate the immune response. This review will summarize the structure of laminins, the modulation of their expression, and their interactions with the immune system...
July 3, 2017: Trends in Immunology
Alexander Kurilshikov, Cisca Wijmenga, Jingyuan Fu, Alexandra Zhernakova
The mammalian gut is colonized by trillions of microorganisms collectively called the microbiome. It is increasingly clear that this microbiome has a critical role of in many aspects of health including metabolism and immunity. While environmental factors such as diet and medications have been shown to influence the microbiome composition, the role of host genetics has only recently emerged in human studies and animal models. In this review, we summarize the current state of microbiome research with an emphasis on the effect of host genetics on the gut microbiome composition...
June 29, 2017: Trends in Immunology
Chao Wang, Meromit Singer, Ana C Anderson
Chronic viral infections and cancer often lead to the emergence of dysfunctional or 'exhausted' CD8(+) T cells, and the restoration of their functions is currently the focus of therapeutic interventions. In this review, we detail recent advances in the annotation of the gene modules and the epigenetic landscape associated with T-cell dysfunction. Together with analysis of single-cell transcriptomes, these findings have enabled a deeper and more precise understanding of the transcriptional mechanisms that induce and maintain the dysfunctional state and highlight the heterogeneity of CD8(+) T-cell phenotypes present in chronically inflamed tissue...
June 26, 2017: Trends in Immunology
Florent Ginhoux, Camille Bleriot, Marc Lecuit
No abstract text is available yet for this article.
June 19, 2017: Trends in Immunology
Abhishek D Garg, Pierre G Coulie, Benoit J Van den Eynde, Patrizia Agostinis
Cancer immunotherapy is experiencing a renaissance spearheaded by immune checkpoint inhibitors (ICIs). This has spurred interest in 'upgrading' existing immunotherapies that previously experienced only sporadic success, such as dendritic cells (DCs) vaccines. In this review, we discuss the major molecular, immunological, and clinical determinants of existing first- and second-generation DC vaccines. We also outline the future trends for next-generation DC vaccines and describe their major hallmarks and prerequisites necessary for high anticancer efficacy...
June 10, 2017: Trends in Immunology
Lorenzo Galluzzi, Takahiro Yamazaki, Sandra Demaria
Two resource articles recently published in Cell demonstrate that the elevated phenotypic complexity of the immune infiltrate in human lung adenocarcinomas and renal cell carcinomas can be reliably dissected with mass cytometry. These findings may pave the way to a new era of precision cancer immunotherapy.
June 8, 2017: Trends in Immunology
Noemia S Lima, Morgane Rolland, Kayvon Modjarrad, Lydie Trautmann
The recent Zika virus (ZIKV) epidemic has created an urgent need for a safe and effective vaccine. There is still a dearth of knowledge about ZIKV immunity, but years of investigation into the immunobiology of other flaviviruses has helped to accelerate the development of a ZIKV vaccine. Although the humoral immune response generates the primary correlate of protection from disease, robust T cell responses could enhance ZIKV vaccine efficacy. Additionally, pre-existing immunity to related flaviviruses could generate cross-reactive T cells that may affect immune responses upon vaccination...
June 1, 2017: Trends in Immunology
Etienne Meunier, Petr Broz
The recognition of cellular damage caused by either pathogens or abiotic stress is essential for host defense in all forms of life in the plant and animal kingdoms. The NOD-like receptors (NLRs) represent a large family of multidomain proteins that were initially discovered for their role in host defense in plants and vertebrates. Over recent years the wide distribution of NLRs among metazoans has become apparent and their origins have begun to emerge. Moreover, intense study of NLR function has shown that they play essential roles beyond pathogen recognition - in the regulation of antigen presentation, cell death, inflammation, and even in embryonic development...
May 31, 2017: Trends in Immunology
Laura M Snell, Tracy L McGaha, David G Brooks
Type I interferons (IFN-Is) are emerging as key drivers of inflammation and immunosuppression in chronic infection. Control of these infections requires IFN-I signaling; however, prolonged IFN-I signaling can lead to immune dysfunction. IFN-Is are also emerging as double-edged swords in cancer, providing necessary inflammatory signals, while initiating feedback suppression in both immune and cancer cells. Here, we review the proinflammatory and suppressive mechanisms potentiated by IFN-Is during chronic virus infections and discuss the similar, newly emerging dichotomy in cancer...
May 31, 2017: Trends in Immunology
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