Human Immunology News Volume 5.05 | Feb 7 2017

TOP STORY

New Type of T-Cell Identified as ‘Key Player’ in Development of Rheumatoid Arthritis

Scientists describe a new type of T-cell with a unique pattern of behavior in rheumatoid arthritis (RA)-affected synovial tissues. These ‘peripheral helper’ T-cells, or T_ph cells, are similar to the follicular helper T-cells (T_fh cells) that induce B-cell differentiation within lymph nodes. However, T_ph cells are genetically distinct from T_fh cells, and crucially, they are able to migrate to RA-affected joint tissue, where they can interact with B-cells locally. [Press release from the University of Birmingham discussing online prepublication in Nature] Press Release | Abstract

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A Distinct Innate Lymphoid Cell Population Regulates Tumor-Associated T Cells

Researchers identified a unique innate lymphoid cell population that inhibits tumor-infiltrating lymphocytes from high-grade serous tumors, defined their suppressive capacity in vitro, and performed a comprehensive analysis of their phenotype. [Nat Med] Abstract | Press Release

Drugs and Drug-Like Molecules Can Modulate the Function of Mucosal-Associated Invariant T Cells

Investigators identified a range of small organic molecules, drugs, drug metabolites and drug-like molecules, including salicylates and diclofenac, as MR1-binding ligands. Some of these ligands inhibited mucosal-associated invariant T cells ex vivo and in vivo, while others, including diclofenac metabolites, were agonists. [Nat Immunol] Abstract | Press Release

Neutrophils Acquire Antigen Presentation Capacity to Memory CD4⁺ T Cells In Vitro and Ex Vivo

The authors demonstrated that freshly isolated human neutrophils can function as antigen presenting cells to memory CD4⁺ T cells. Neutrophils pulsed with the cognate antigens CMV pp65 or influenza hemagglutinin were able to present the antigens to autologous antigen-specific CD4⁺ T cells in an MHC class II-dependent manner. [Blood] Abstract

Chloroquine Inhibits Human CD4⁺ T-Cell Activation by AP-1 Signaling Modulation

Researchers evaluated the influence of chloroquine (CQ) on activation parameters of human CD4⁺ T-cells. CQ directly suppressed proliferation, metabolic activity and cytokine secretion of T-cells following anti-CD3/anti-CD28 activation. [Sci Rep] Full Article

Altered Expression of miR-181a and miR-146a Does Not Change the Expression of Surface NCRs in Human NK Cells

Scientists predicted microRNA (miR)-181a to regulate the expression of the natural cytotoxicity receptor NCR2 by seeded interaction with the 3′-untranslated region. Whereas miR-146a expression was not significantly different, miR-181a expression was, on average 10-fold lower in NK cells from breast cancer patients compared to normal subjects. [Sci Rep] Full Article

CD31, a Valuable Marker to Identify Early and Late Stages of T Cell Differentiation in the Human Thymus

The authors provide a global picture of the evolution of CD31 expression from the CD34⁺ hematopoietic precursor to the CD45RA⁺ mature CD4⁺ and CD8⁺ single-positive T cells. [J Immunol] Abstract

Predominant Contribution of DGKζ over DGKα in the Control of PKC/PDK-1-Regulated Functions in T Cells

Investigators used siRNA-mediated gene silencing in human T cells and diacylglycerol kinase (DGK)α- and DGKζ-deficient mice to define DGK isoform-specific regulation of key signaling pathways during T cell activation. They identified DGKζ as the predominant brake on basal/tonic conditions as well as on downstream T cell receptor/co-stimulatory signals. [Immunol Cell Biol] Abstract

IL-10-Producing, ST2-Expressing Foxp3⁺ T Cells in Multiple Sclerosis Brain Lesions

The authors showed that Foxp3⁺ cells in the brains of multiple sclerosis patients predominantly produce interleukin (IL)-10 and show high expression of the IL-33 receptor ST2, indicating that T regulatory in the inflamed brain maintain their suppressive function. [Immunol Cell Biol] Abstract

Rapid De Novo Generation of Antigen Specific Human B Cells with Expression of Blimp-1 and AID by In Vitro Immunization

Investigators demonstrated a novel method for de novo inducing antigen-specific human B cells in vitro. Unlike previous in vitro immunization of unfractionated peripheral blood mononuclear cells, they first optimized the conditions for inducing monocyte-derived dendritic cells to efficiently capture, process, and present antigens. [Exp Cell Res] Abstract

Silymarin Suppresses Basal and Stimulus-Induced Activation, Exhaustion, Differentiation, and Inflammatory Markers in Primary Human Immune Cells

Silymarin (SM) treatment suppressed the expression of T cell activation and exhaustion markers on CD4⁺ and CD8⁺ T cells from chronically-infected, HIV-positive subjects. SM also showed a trend towards modifying CD4⁺ T cell memory subsets from HIV⁺ subjects. [PLoS One] Full Article

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Melatonin Signaling in T Cells: Functions and Applications

The authors focus on the current understanding of the significance of melatonin in T cell biology and the beneficial effects of melatonin in T cell response-based diseases. In addition to expressing both membrane and nuclear receptors for melatonin, T cells have the four enzymes required for the synthesis of melatonin and produce high levels of melatonin. [J Pineal Res] Abstract

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Kiadis Pharma Issues Clinical and Regulatory Progress Update on ATIR101™ and ATIR201™

Kiadis Pharma N.V. provided a progress update on the clinical and regulatory status of ATIR101™, the company’s lead product to address the key risks and limitations of hematopoietic stem cell transplantation in blood cancer. [Kiadis Pharma N.V.] Press Release

Bristol-Myers Squibb Receives FDA Approval for Opdivo (Nivolumab) in Previously Treated Locally Advanced or Metastatic Urothelial Carcinoma, a Type of Bladder Cancer

Bristol-Myers Squibb Company announced the U.S. Food and Drug Administration (FDA) has approved Opdivo injection, for intravenous use for the treatment of patients with locally advanced or metastatic urothelial carcinoma who have disease progression during or following platinum-containing chemotherapy or have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy. [Bristol-Myers Squibb Company] Press Release

Protagen AG Join Forces with the U.S. National Cancer Institute to Answer Pressing Questions in Immuno-Oncology

Protagen AG has executed a Material Transfer Agreement with the National Cancer Institute under which the parties will utilize Protagens SeroTag^® immune system profiling technology to identify biomarkers that predict therapy responsiveness, to monitor patients receiving immunotherapies, and for early detection of immune-related adverse events. [Protagen AG] Press Release

Personal Genome Diagnostics Awarded National Cancer Institute Contract to Develop Novel Diagnostic for Immuno-Oncology Drugs

Personal Genome Diagnostics Inc. announced that it has been awarded an SBIR contract from the National Cancer Institute for the development of a novel diagnostic to help identify patients who are most likely to benefit from treatment with immuno-oncology cancer drugs known as checkpoint inhibitors. [Personal Genome Diagnostics Inc.] Press Release

Study Retraction Reignites Concern over China’s Possible Use of Prisoner Organs

A journal has decided to retract a 2016 study because of concerns that its data on the safety of liver transplantation involved organs sourced from executed prisoners in China. The action, taken despite a denial by the study’s authors that such organs were used, comes after clinical ethicist Wendy Rogers of Macquarie University in Sydney, Australia, and colleagues authored a letter to the editor of Liver International, calling for the paper’s retraction in the “absence of credible evidence of ethical sourcing of organs.” [ScienceInsider] Editorial

Biotech Bosses Protest Trump’s Travel Ban

In a letter published in Nature Biotechnology, 166 biotech execs leveled a blast at Trump’s travel ban, now stayed at least temporarily by a court ruling, saying that it strikes at the heart of the industry’s ability to recruit the best and brightest staff from all over the world while raising deep seated fears among all their staffers from outside the US. [ScienceInsider] Editorial

US Government Takes Animal-Welfare Data Offline

The US Department of Agriculture agency charged with ensuring the humane treatment of large research animals, such as primates and goats, has quietly scrubbed all inspection reports and enforcement records from its website. The move has drawn criticism from animal-welfare and transparency activists who say the public has the right to know how their tax dollars are being used. [Nature News] Editorial

Venezuela Is Running Short on HIV Meds—and Places to Turn for Help

On top of its currency being in free fall for three years running, empty shelves at supermarkets, and electricity rationing, Venezuela has a serious shortage of medicines, including life-saving anti-HIV drugs. This led a network of Venezuelans living with HIV to seek “urgent humanitarian aid” in June 2016 from the Geneva, Switzerland–based Global Fund to Fight AIDS, Tuberculosis and Malaria. [ScienceInsider] Editorial

NEW Keystone Symposium: B Cells and T Follicular Helper Cells – Controlling Long-Lived Immunity
April 23-27, 2017
Whistler, Canada

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