Human Immunology News Volume 4.44 | Nov 8 2016

TOP STORY

S-2-Hydroxyglutarate Regulates CD8⁺ T-Lymphocyte Fate

Scientists showed that CD8⁺ T-lymphocytes accumulate 2-hydroxyglutarate in response to T-cell receptor triggering. This increases to millimolar levels in physiological oxygen conditions, via a hypoxia inducible factor 1 alpha-dependent mechanism. [Nature] Abstract | Press Release

(Ranked by impact factor of the journal)

Differential Effects of Environmental and Genetic Factors on T and B Cell Immune Traits

Investigators used a systems biology approach to comprehensively assess the impact of environmental and genetic factors on immune cell populations in peripheral blood, including associations with immunoglobulin concentrations, from ~500 healthy volunteers from the Human Functional Genomics Project. [Cell Rep] Full Article | Graphical Abstract

Inflammatory Cues Enhance TGFβ Activation by Distinct Subsets of Human Intestinal Dendritic Cells via Integrin αvβ8

Scientists showed that a key activator of transforming growth factor-β (TGFβ), integrin αvβ8, is highly expressed on human intestinal dendritic cells (DCs), specifically on the CD1c⁺ but not the CD141⁺ intestinal DC subset. [Mucosal Immunol] Full Article

IL-25 Attenuates Rheumatoid Arthritis through Suppression of Th17 Immune Responses in an IL-13-Dependent Manner

Researchers aimed to analyze IL-25 expression in the serum and synovial fluid of rheumatoid arthritis (RA) patients and evaluated the correlations between serum IL-25 levels, clinical and laboratory values and inflammation cytokines. Additionally, they investigated whether IL-25 can suppress Th1/Th17 responses involved in RA pathogenesis. [Sci Rep] Full Article

Reconstituted B Cell Receptor Signaling Reveals Carbohydrate-Dependent Mode of Activation

Using a new approach to reconstitute antigen-receptor interactions in a human reporter B cell line, scientists found that sequence-defined B cell receptors (BCRs) from the human germline repertoire could be triggered by both complementarity to influenza hemagglutinin and a separate mode of signaling that relied on multivalent ligation of BCR sialyl-oligosaccharide. [Sci Rep] Full Article

Expansion of Th17 Cells by Human Mast Cells Is Driven by Inflammasome-Independent IL-1β

The authors determined the effect of mast cells (MC) on cytokine production by naive and memory human Th cells. CD4⁺ T cells were cultured with MC supernatant or control medium, after which cytokine production by T cells was determined. [J Immunol] Abstract

CD8⁺ T-Cell Specificity Is Compromised at a Defined MHCI/CD8 Affinity Threshold

Scientists used a panel of major histocompatibility complex class I (MHCI) mutants with altered CD8-binding properties to show that T-cell receptor-mediated antigen specificity is delimited by a peptide-MHCI/CD8 affinity threshold. [Immunol Cell Biol] Full Article

Effect of Growth Hormone and IgG Aggregates on Dendritic Cells Activation and T-Cells Polarization

Maturation of human monocyte-derived dendritic cells (moDC) upon exposure to native biological products or aggregates was evaluated in vitro. Results showed that human growth hormone aggregates induced an increased expression of moDC co-stimulation markers, and augmented levels of IL-6, IL-8, IL-12p40, CCL2, CCL3, CCL4 and CXCL10. [Immunol Cell Biol] Abstract

Treatment of Human B-Cell Lymphomas Using Minicircle DNA Vector Expressing Anti-CD3/CD20 in a Mouse Model

Investigators present concept-proving data that problems could be bypassed by using an enhanced nonviral DNA vector minicircle to produce bispecific antibodies in vivo. They found that the anti-CD3/CD20 produced from the minicircle could effectively mediate the T-cell killing of multiple CD20-positive human B-cell lymphoma cell lines in vitro. [Hum Gene Ther] Abstract

Distinctive Regulatory T Cells and Altered Cytokine Profile Locally in the Airways of Young Smokers with Normal Lung Function

Scientists characterized the frequencies and characteristics of CD4⁺ and CD8⁺ T cell subsets in the blood and lungs of young tobacco smokers. Bronchoalveolar lavage and peripheral blood were obtained from healthy moderate smokers and never-smokers, all with normal lung function. [PLoS One] Full Article

Characterization of γδ Regulatory T Cells from Peripheral Blood in Patients with Multiple Myeloma

The authors investigated the potential role of γδ regulatory T cells in inhibiting anti-tumor immune responses in patients diagnosed as multiple myeloma (MM). They measured the levels of γδ T cells, the distribution and clonally amplified TCR Vγ and VδT cells in peripheral blood of healthy donors, patients recently diagnosed with MM, and MM patients in remission cohorts. [Biochem Biophys Res Commun] Abstract

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Impact of Inhibitor of Apoptosis Proteins on Immune Modulation and Inflammation

The authors focus on modulation of the innate and adaptive immune systems, macrophage plasticity and inflammatory responses by inhibitors of apoptosis (IAP) family members. They also explore the rationale to target IAPs pharmacologically for the treatment of a number of inflammatory diseases and cancer. [Immunol Cell Biol] Full Article

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Ascend Biopharmaceuticals Announces Encouraging Phase I/IIa Interim Results of ASN-002 Treatment of Nodular Basal Cell Carcinoma (nBCC)

Ascend Biopharmaceuticals Ltd. announced interim results from the first nine patient of its Phase I/IIa clinical trial evaluating the safety and clinical activity of its lead candidate, ASN-002. [Ascend Biopharmaceuticals Ltd.] Press Release

DNAtrix Announces First Patients Treated in Phase II Trial with DNX-2401 and KEYTRUDA

DNAtrix announced that the first patients have been treated in a multicenter Phase II trial investigating its oncolytic adenovirus, DNX-2401, in combination with KEYTRUDA^®, Merck’s anti-PD-1 therapy, in patients with recurrent glioblastoma. [DNAtrix] Press Release

CryoVax^®: Next Generation Immunotherapy for Metastatic Colorectal Cancer Begins USA Phase IIb Clinical Trial

Immunovative Therapies, Ltd., on behalf of its’ subsidiary, ImmunoCare, Ltd., announced the start of a Phase IIb study of CryoVax^®, a next generation immunotherapy cancer vaccine product, for patients with chemotherapy-refractory metastatic colorectal cancer. [Immunovative Therapies, Ltd.] Press Release

Big Brain Projects Urged to Aid Public Health

Major brain-mapping projects have multiplied in recent years, as neuroscientists develop new technologies to decipher how the brain works. These initiatives focus on understanding the brain, but the World Health Organization wants to ensure that they work to translate their early discoveries and technological advances into tests and treatments for brain disorders. [Nature News] Editorial

On Election Day, Science also on the Ballot in Some States

Voters who go to the polls on Tuesday will not just choose the next president and other lawmakers. They will also weigh in on some 154 state ballot initiatives on topics ranging from gun control and marijuana legalization to minimum wage increases and environmental policy. [Science Insider] Editorial

Hard Work, Little Reward: Nature Readers Reveal Working Hours and Research Challenges

A poll answered by thousands of Nature readers suggests that nearly two-thirds have considered quitting research, and that almost 40% work more than 60 hours in a week. The fight for funding is the greatest challenge facing early-career scientists, readers said. [Nature] Editorial

Twitterstorm Shows Why Scientific Evidence Matters

Grammar and Twitter rarely sit happily, so it would be churlish to point out that when the Welsh MP Glyn Davies tweeted at the weekend: “Nothing more irritating than academics ­rubbishing the efforts of those operating at the sharp end, without facing up to the hard decisions”, he was inadvertently complaining that people at the sharp end (himself included presumably) do not confront hard decisions. [Nature] Editorial

Russian Science at the Crossroads

As the United States goes to the polls after an unprecedentedly vulgar election campaign, its former cold-war rival is exuding strength and confidence. Just last week, Russia cited its proud history of exploration and science in Antarctica when giving the green light to an international agreement to create a vast marine reserve in the Ross Sea. [Nature News] Editorial

Tracker Flags Up Failures to Report Clinical Trials

An automated tool has trawled through thousands of records on the world’s leading clinical-trials database to reveal which drug firms and academic institutions are failing to publish the results of their trials. The US Department of Health and Human Services announced tougher rules to push the researchers that it funds to publish clinical-trial designs and results. [Nature News] Editorial

NEW American Academy of Allergy, Asthma & Immunology (AAAAI) Annual Meeting
March 3-6, 2017
Atlanta, United States

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NEW Postdoctoral Position – Development of Immune System (Lund University)

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Faculty Positions – Immunology (Ohio State University)

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