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Daria Esterházy, Jakob Loschko, Mariya London, Veronica Jove, Thiago Y Oliveira, Daniel Mucida
Oral tolerance prevents pathological inflammatory responses to innocuous foreign antigens by peripheral regulatory T cells (pT(reg) cells). However, whether a particular subset of antigen-presenting cells (APCs) is required during dietary antigen exposure for the 'instruction' of naive CD4(+) T cells to differentiate into pT(reg) cells has not been defined. Using myeloid lineage-specific APC depletion in mice, we found that monocyte-derived APCs were dispensable, while classical dendritic cells (cDCs) were critical, for pT(reg) cell induction and oral tolerance...
May 2016: Nature Immunology
Marta Teperek, Angela Simeone, Vincent Gaggioli, Kei Miyamoto, George E Allen, Serap Erkek, Taejoon Kwon, Edward M Marcotte, Philip Zegerman, Charles R Bradshaw, Antoine H F M Peters, John B Gurdon, Jerome Jullien
For a long time, it has been assumed that the only role of sperm at fertilization is to introduce the male genome into the egg. Recently, ideas have emerged that the epigenetic state of the sperm nucleus could influence transcription in the embryo. However, conflicting reports have challenged the existence of epigenetic marks on sperm genes, and there are no functional tests supporting the role of sperm epigenetic marking on embryonic gene expression. Here, we show that sperm is epigenetically programmed to regulate embryonic gene expression...
August 2016: Genome Research
Randall J Brezski, George Georgiou
Monoclonal antibody-based drugs continue to be one of the most rapidly growing classes of therapeutic molecules. At present, the majority of approved therapeutic antibodies are of the human IgG1 format, which can elicit immune effector functions (e.g., antibody-dependent cellular cytotoxicity, antibody-dependent cellular phagocytosis, and complement-dependent cytotoxicity). However, there is a wealth of functional diversity that is present in other isotypes and IgG subclasses that can be exploited to improve clinical safety and performance by increasing stability, reduction of adverse events, modulation of effector functions, and by the engagement of two antigens by a single antibody...
June 2016: Current Opinion in Immunology
Peter Sondermann, David E Szymkowski
The antibody Fc domain engages the small family of Fc receptors, expressed on cells of the immune system and beyond, to stimulate a rich diversity of positive and negative cell-mediated effector functions. The emergence of monoclonal antibodies for the treatment of various pathologic conditions has provided additional insights into Fc receptor biology, and has suggested new strategies to exploit Fc receptor interactions to create improved therapeutics. While most therapeutic IgGs approved to date have retained a native IgG Fc domain, the knowledge gained over the last decades has provided the opportunity to design tailored and more efficacious immunotherapies exhibiting fewer side effects and longer half-life...
June 2016: Current Opinion in Immunology
Sandeep Kumar Dhanda, Salman Sadullah Usmani, Piyush Agrawal, Gandharva Nagpal, Ankur Gautam, Gajendra P S Raghava
The conventional approach for designing vaccine against a particular disease involves stimulation of the immune system using the whole pathogen responsible for the disease. In the post-genomic era, a major challenge is to identify antigenic regions or epitopes that can stimulate different arms of the immune system. In the past two decades, numerous methods and databases have been developed for designing vaccine or immunotherapy against various pathogen-causing diseases. This review describes various computational resources important for designing subunit vaccines or epitope-based immunotherapy...
May 1, 2017: Briefings in Bioinformatics
Huiyun Wang, Xuexin Zhang, Li Xue, Juan Xing, Marie-Hélène Jouvin, James W Putney, Matthew P Anderson, Mohamed Trebak, Jean-Pierre Kinet
Activation of T cells is mediated by the engagement of T cell receptors (TCRs) followed by calcium entry via store-operated calcium channels. Here we have shown an additional route for calcium entry into T cells-through the low-voltage-activated T-type CaV3.1 calcium channel. CaV3.1 mediated a substantial current at resting membrane potentials, and its deficiency had no effect on TCR-initiated calcium entry. Mice deficient for CaV3.1 were resistant to the induction of experimental autoimmune encephalomyelitis and had reduced productions of the granulocyte-macrophage colony-stimulating factor (GM-CSF) by central nervous system (CNS)-infiltrating T helper 1 (Th1) and Th17 cells...
April 19, 2016: Immunity
Ralf Jungmann
No abstract text is available yet for this article.
April 2016: Nature Methods
Petro Starokadomskyy, Terry Gemelli, Jonathan J Rios, Chao Xing, Richard C Wang, Haiying Li, Vladislav Pokatayev, Igor Dozmorov, Shaheen Khan, Naoteru Miyata, Guadalupe Fraile, Prithvi Raj, Zhe Xu, Zigang Xu, Lin Ma, Zhimiao Lin, Huijun Wang, Yong Yang, Dan Ben-Amitai, Naama Orenstein, Huda Mussaffi, Eulalia Baselga, Gianluca Tadini, Eyal Grunebaum, Adrijan Sarajlija, Konrad Krzewski, Edward K Wakeland, Nan Yan, Maria Teresa de la Morena, Andrew R Zinn, Ezra Burstein
Aberrant nucleic acids generated during viral replication are the main trigger for antiviral immunity, and mutations that disrupt nucleic acid metabolism can lead to autoinflammatory disorders. Here we investigated the etiology of X-linked reticulate pigmentary disorder (XLPDR), a primary immunodeficiency with autoinflammatory features. We discovered that XLPDR is caused by an intronic mutation that disrupts the expression of POLA1, which encodes the catalytic subunit of DNA polymerase-α. Unexpectedly, POLA1 deficiency resulted in increased production of type I interferons...
May 2016: Nature Immunology
Praveen Paul, Michael Motskin
Effectively communicating science and linking it to the 'real world' has important benefits for both scientists and society. Here we share our experience at Pint of Science, an initiative that encourages researchers to discuss their findings with the public and to engage in conversation in a relaxed setting. We discuss strategies towards organizing a scientific outreach event - big or small - and encourage you to get involved in a science festival near you.
April 2016: Trends in Immunology
Hiroki Ando, Sebastien Lemire, Diana P Pires, Timothy K Lu
Bacteria are central to human health and disease, but existing tools to edit microbial consortia are limited. For example, broad-spectrum antibiotics are unable to accurately manipulate bacterial communities. Bacteriophages can provide highly specific targeting of bacteria, but assembling well-defined phage cocktails solely with natural phages can be a time-, labor- and cost-intensive process. Here, we present a synthetic-biology strategy to modulate phage host ranges by engineering phage genomes in Saccharomyces cerevisiae...
September 23, 2015: Cell Systems
Susanne H Baumeister, Gordon J Freeman, Glenn Dranoff, Arlene H Sharpe
The immune system is capable of recognizing tumors and eliminates many early malignant cells. However, tumors evolve to evade immune attack, and the tumor microenvironment is immunosuppressive. Immune responses are regulated by a number of immunological checkpoints that promote protective immunity and maintain tolerance. T cell coinhibitory pathways restrict the strength and duration of immune responses, thereby limiting immune-mediated tissue damage, controlling resolution of inflammation, and maintaining tolerance to prevent autoimmunity...
May 20, 2016: Annual Review of Immunology
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