Human Immunology News Volume 5.31 | Aug 8 2017

TOP STORY

A Phenotypically and Functionally Distinct Human T_H2 Cell Subpopulation Is Associated with Allergic Disorders

Scientists described a subset of human memory type 2 helper T (T_H2) cells confined to atopic individuals that includes all allergen-specific T_H2 cells. These cells were terminally differentiated CD4⁺ T cells characterized by coexpression of CRT_H2, CD49d, and CD161 and exhibited numerous functional attributes distinct from conventional T_H2 cells. [Sci Transl Med] Abstract | Press Release | Editorial | Video

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GSK 3 Inhibition Drives Maturation of NK Cells and Enhances Their Antitumor Activity

Researchers showed that pharmacological inhibition of GSK3 kinase in peripheral blood natural killer (NK) cells expanded ex vivo with IL-15 greatly enhanced CD57 upregulation and late-stage maturation. GSK3 inhibition elevated the expression of several transcription factors associated with late-stage NK cell maturation including T-BET, ZEB2 and BLIMP-1 without affecting viability or proliferation. [Cancer Res] Abstract | Press Release

B. abortus RNA Is the Component Involved in the Down-Modulation of MHC-I Expression on Human Monocytes via TLR8 and the EGFR Pathway

Researchers demonstrated that the down-modulation of MHC-I expression is not mediated by well-known Brucella virulence factors but instead by Brucella abortus RNA, a PAMP associated to viability. [PLoS Pathog] Full Article

Salmonella typhimurium-Induced IL-1 Release from Primary Human Monocytes Requires NLRP3 and Can Occur in the Absence of Pyroptosis

The authors investigated the effect of S. typhimurium on inflammasomes in primary human monocytes. They reported that inhibiting NLRP3 with the selective inhibitor MCC950, blocked release of IL-1β and the related cytokine IL-1α from primary human monocytes in response to S. typhimurium. [Sci Rep] Full Article

Phosphatidylinositol 3-Kinase Inhibition Potentiates Glucocorticoid Response in B-Cell Acute Lymphoblastic Leukemia

Researchers analyzed the therapeutic potential of pan and isoform-selective phosphatidylinositol 3-kinase (PI3K) p110 inhibitors, alone or combined with dexamethasone, in B-cell acute lymphoblastic leukemia (B-ALL) leukemia cell lines and patient samples. They found that a pan PI3K p110 inhibitor displayed the most powerful cytotoxic effects in B-ALL cells, by inducing cell cycle arrest and apoptosis. [J Cell Physiol] Abstract

Human Regulatory Macrophages Are Potent in Suppression of the Xenoimmune Response via Indoleamine-2,3-Dioxygenase-Involved Mechanism(s)

Scientists assessed the potential of human regulatory macrophages (Mregs) to be used as an effective immunomodulatory method in xenotransplantation. They demonstrated that human Mregs are capable of suppressing the xenoimmune response in vitro via indoleamine-2,3-dioxygenase-involved mechanism(s), suggesting their potential role as an effective immunomodulatory tool in xenotransplantation. [Xenotransplantation] Abstract

Human Endogenous Retrovirus HERV-K(HML-2) Env Expression Is Not Associated with Markers of Immunosenescence

The authors evaluated the role of the evolutionary youngest group of human endogenous retroviruses, namely HERV-K(HML-2), on immunosenescence. HERVs exist in the genome as proviruses, but their activation has been detected in several immunopathologic conditions. The expression of HERV-K(HML-2) env was observed to be lower in the peripheral blood mononuclear cells of nonagenarians than in those of young controls. [Exp Gerontol] Abstract

Physiological Doses of Red Light Induce IL-4 Release in Co-Cultures between Human Keratinocytes and Immune Cells

Investigators delivered calibrated doses of well-defined light qualities to co-cultures of human keratinocytes and macrophage/dendritic cells in the absence or presence of the commonly used photosensitizer 8-methoxypsoralen (8-MOP). The experiments identified IL-4 as a key effector cytokine released by this co-culture model with need for 8-MOP in the UVA₁/blue and no requirement for photosensitizer in the red light spectrum. [Photochem Photobiol] Abstract

Recovery from the Middle East Respiratory Syndrome Is Associated with Antibody and T-Cell Responses

The authors obtained peripheral blood mononuclear cells and/or sera from 21 Middle East respiratory syndrome (MERS) survivors. They detected MERS-coronavirus–specific CD4⁺ and CD8⁺ T cell responses in all MERS survivors and demonstrated functionality by measuring cytokine expression after peptide stimulation. [Sci Immunol] Full Article

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Novel Therapies for Immune-Mediated Inflammatory Diseases: What Can We Learn from Their Use in Rheumatoid Arthritis, Spondyloarthritis, Systemic Lupus Erythematosus, Psoriasis, Crohn’s Disease and Ulcerative Colitis?

Investigators review novel biologic agents targeting the T-helper 17 axis. They present an overview of biologics active against type I and II interferons. They summarize the development and recent application of Janus kinase (JAK) inhibitors in the treatment of immune-mediated inflammatory diseases. [Ann Rheum Dis] Abstract

Clinical Development of CAR T Cells—Challenges and Opportunities in Translating Innovative Treatment Concepts

Scientists provide a comprehensive overview of the clinical trials performed so far worldwide and analyze parameters such as targeted antigen and indication, chimeric antigen receptor (CAR) molecular design, CAR T cell manufacturing, anti-tumor activities, and related toxicities. [EMBO Mol Med] Full Article

T Helper Type 17 Cells in Immune-Mediated Glomerular Disease

Investigators describe the identification, regulation, and function of T helper type 17 cells and their associated pathways in immune-mediated kidney diseases, with a particular focus on the mechanisms underlying renal tissue injury. [Nat Rev Nephrol] Abstract

Mevalonate Metabolism Governs Cancer Immune Surveillance

The authors address how mevalonate metabolism drives immunity and highlight ways the immune system responds to both, limited and uncontrolled flux through the mevalonate pathway. [Oncoimmunology] Abstract | Full Article

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Kite Doses First Patient in the Phase II Trial of Axicabtagene Ciloleucel in Indolent B-Cell Non-Hodgkin Lymphoma (ZUMA-5)

Kite Pharma, Inc. announced that patients with relapsed/refractory indolent B-cell non-Hodgkin lymphoma are now being treated in its Phase II ZUMA-5 trial with its lead investigational candidate, axicabtagene ciloleucel. [Kite Pharma, Inc.] Press Release

Kite Files the Industry’s First CAR-T Marketing Authorization Application in Europe for Axicabtagene Ciloleucel

Kite Pharma, Inc. announced that it has submitted a Marketing Authorization Application to the European Medicines Agency for axicabtagene ciloleucel as a treatment for patients with relapsed/refractory diffuse large B-cell lymphoma, transformed follicular lymphoma, and primary mediastinal B-cell lymphoma who are ineligible for autologous stem cell transplant. [Kite Pharma, Inc.] Press Release

VistaGen Receives Notice of Allowance from U.S. Patent and Trademark Office for U.S. Patent Regarding Breakthrough Methods for Producing Blood Cells, Platelets and Bone Marrow Stem Cells with Potential to Treat Autoimmune Disorders and Cancer

VistaGen Therapeutics Inc. announced that the company has received a Notice of Allowance from the U.S. Patent and Trademark Office for U.S. Patent Application No. 14/359,517 regarding proprietary methods for producing hematopoietic precursor stem cells with potential to impact both direct and supportive therapy for autoimmune disorders and cancer. [VistaGen Therapeutics Inc.] Press Release

TARGET PharmaSolutions Enrolls First Participant in Its Inflammatory Bowel Disease (IBD) Community

TARGET PharmaSolutions, Inc. announced the enrollment of the first participant in its IBD community, TARGET-IBD, which includes adult and pediatric patients with ulcerative colitis, Crohn’s disease and indeterminate colitis. [TARGET PharmaSolutions, Inc.] Press Release

FDA Advisory Committee Does Not Recommend Approval of Sirukumab for the Treatment of Moderately to Severely Active Rheumatoid Arthritis

Janssen Biotech, Inc. announced that the Arthritis Advisory Committee of the U.S. FDA did not recommend approval of sirukumab for the treatment of moderately to severely active rheumatoid arthritis in adults who have had an inadequate response or are intolerant to one or more disease modifying anti-rheumatic drugs. [Janssen Biotech, Inc.] Press Release

FDA Cracks Down on Pioneering Doctor Who Created a Three-Parent Baby

The New York-based doctor who helped a couple have a child using DNA from three people has been told by the FDA that he can’t go ahead with clinical trials meant to test the technique. [MIT Technology Review] Editorial

CRISPR Patent Battle in Europe Takes a ‘Wild’ Twist with Surprising Player

MilliporeSigma, a subsidiary of pharmaceutical giant Merck KGaA of Darmstadt, Germany, has become a new major player in the complicated European patent battles over CRISPR, the revolutionary genome-editing tool. [ScienceInsider] Editorial

Chronic Diseases Spike in Middle East as Conflicts Rage

Across the Middle East, deaths resulting from violence grew by 850% between 1990 and 2015, according to a series of reports published in the International Journal of Public Health. The increase accelerated after 2010, corresponding with the beginning of the Arab Spring movement and wars in Syria and Iraq. At the same time, the authors found, the incidence of many chronic diseases has also risen dramatically. [Nature News] Editorial

Drug Approval Needs a Helping Hand

It’s time for researchers to lend their expertise to expediting the arrival of cutting-edge therapies that are waiting in the wings. [Nature News] Editorial

Discredited Gene-Editing Researcher Vows to Clear His Name

A Chinese biologist whose team retracted a high-profile paper on a gene-editing technology has vowed to press ahead with experiments that he hopes will vindicate the potential rival to the CRISPR/Cas9 system. [ScienceInsider] Editorial

NEW Keystone Symposia: Translational Systems Immunology
January 28-February 1, 2018
Snowbird, Utah, United States

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NEW Postdoctoral Fellowships – Immune Signaling and Metabolism (St. Jude Children’s Research Hospital)

NEW Postdoctoral Research Fellow – Immunology (Harvard Medical School, Joslin Diabetes Center)

Postdoctoral Researcher – Inflammatory Diseases (University of Pennsylvania)

Assistant Professor – Cell Science (University of Manitoba)

Postdoctoral Research Associate – Autoimmune Disease Research (Benaroya Research Institute at Virginia Mason)

Postdoctoral Fellow – B Cells in Autoimmune Diseases (Inserm)

Postdoctoral Fellow – Inflammatory Autoimmune Disease (Vanderbilt University Medical Center)

Postdoctoral Position – Molecular Biology and Immunology (Harvard Medical School)

Postdoctoral Research Fellow – Cancer Immunotherapy (Fred Hutchinson Cancer Research Center)

Postdoctoral Fellow – Neuroimmunology (Duke University)

Postdoctoral Fellow – Cell Biology and Innate Immunity (The Laboratory for Molecular Infection Medicine Sweden)

Postdoctoral Fellow – Inflammatory Bowel Disease (Harvard Medical School)

Postdoctoral Research Fellow – Innate Immunity (Fred Hutchinson Cancer Research Center)

Assistant, Associate or Full Member – Cancer Immunology (Fred Hutchinson Cancer Research Center)

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