Volume 5.21 | Jun 7

Immune Regulation News 5.21 June 7, 2013
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BACH2 Represses Effector Programs to Stabilize Treg-Mediated Immune Homeostasis
By studying mice in which the Bach2 gene is disrupted, researchers defined BACH2 as a broad regulator of immune activation that stabilizes immunoregulatory capacity while repressing the differentiation programs of multiple effector lineages in CD4+ T cells. BACH2 was required for efficient formation of regulatory (Treg) cells and consequently for suppression of lethal inflammation in a manner that was Treg-cell-dependent. [Nature] Abstract | Press Release

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PUBLICATIONS (Ranked by impact factor of the journal)

Posttranscriptional Control of T Cell Effector Function by Aerobic Glycolysis
Investigators showed that aerobic glycolysis is specifically required for effector function in T cells but that this pathway is not necessary for proliferation or survival. When activated T cells are provided with costimulation and growth factors but are blocked from engaging glycolysis, their ability to produce IFN- is markedly compromised. [Cell] Abstract | Press Release | Video

The Signaling Suppressor CIS Controls Proallergic T Cell Development and Allergic Airway Inflammation
Scientists found that the SOCS protein CIS, which was substantially induced by interleukin 4, negatively regulated the activation of STAT3, STAT5 and STAT6 in T cells. CIS-deficient mice spontaneously developed airway inflammation, and CIS deficiency in T cells led to greater susceptibility to experimental allergic asthma. [Nat Immunol] Abstract

Foxp3 Transcription Factor Is Proapoptotic and Lethal to Developing Regulatory T Cells unless Counterbalanced by Cytokine Survival Signals
Investigators report that Foxp3 was lethal to developing regulatory T (Treg) cells in the thymus because it induced a unique proapoptotic protein signature (Puma++p-Bim++p-JNK++DUSP6) and repressed expression of prosurvival Bcl-2 molecules. However, Foxp3 lethality was prevented by common gamma chain (γc)-dependent cytokine signals that were present in the thymus in limiting amounts sufficient to support only one million Treg cells. [Immunity] Abstract | Graphical Abstract

Antigenic Liposomes Displaying CD22 Ligands Induce Antigen-Specific B Cell Apoptosis
Researchers showed that liposomal nanoparticles, displaying both antigen and glycan ligands of the inhibitory coreceptor CD22, induce a tolerogenic program that selectively causes apoptosis in mouse and human B cells. [J Clin Invest] Full Article | Press Release

Antigen-Specific, Antibody-Coated, Exosome-Like Nanovesicles Deliver Suppressor T-Cell MicroRNA-150 to Effector T Cells to Inhibit Contact Sensitivity
Investigators examined the mechanism or mechanisms of immune suppression mediated by antigen-specific suppressive nanovesicles. T-cell tolerance was induced by means of intravenous injection of hapten conjugated to self-antigens of syngeneic erythrocytes and subsequent contact immunization with the same hapten. [J Allergy Clin Immunol] Abstract

Protection of Islet Grafts through TGF Beta Induced Tolerogenic DC
Scientists investigated the possibilities of transient expression of the immunosuppressive cytokine Transforming Growth Factor (TGF) beta within islets to achieve long term graft tolerance. They found that brief expression of TGF beta prevented rejection of syngeneic islets, that there was reduction of dendritic cell (DC) activation in the graft and reduced reactivation of T cells in the graft draining lymph nodes. [Diabetes] Abstract

MHCII Is Required for α-Synuclein-Induced Activation of Microglia, CD4 T Cell Proliferation, and Dopaminergic Neurodegeneration
Results indicated a central role for microglial MHCII in the activation of both the innate and adaptive immune responses to α-syn in Parkinson disease and suggested that the MHCII signaling complex may be a target of neuroprotective therapies for the disease. [J Neurosci] Abstract | Press Release

Mediation of Protection and Recovery from Experimental Autoimmune Encephalomyelitis by Macrophages Expressing the Human Voltage-Gated Sodium Channel NaV1.5
Investigators previously demonstrated that a variant of the voltage-gated sodium channel NaV1.5 is expressed intracellularly in human macrophages, and that it regulates cellular signaling. This channel is not expressed in mouse macrophages, which has limited the study of its functions. To overcome this obstacle, they developed a novel transgenic mouse model, in which the human macrophage NaV1.5 splice variant is expressed in vivo in mouse macrophages. [J Neuropathol Exp Neurol] Abstract | Press Release

Commensal Microbiota Are Required for Systemic Inflammation Triggered by Necrotic Dendritic Cells
Scientists report that mice deficient for the Fas-associated death domain in dendritic cells (DCs) developed systemic inflammation associated with elevated proinflammatory cytokines and increased myeloid and B cells. These mice exhibited reduced DCs in gut-associated lymphoid tissues due to RIP3-dependent necroptosis, whereas DC functions remained intact. [Cell Rep] Abstract | Graphical Abstract | Full Article

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T Cell Regulation of Natural Killer Cells
In light of their role in the immune response against tumors and viruses, natural killer (NK) cells represent a promising target for immunotherapy. Before this target is reached, the various mechanisms that control NK cell activity must first be identified and understood. [J Exp Med] Abstract

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NewLink Genetics Presents Results from Two Phase I Studies with Immunotherapy Agent, Indoximod
NewLink Genetics Corporation announced results from two clinical studies with indoximod, an orally administered small molecule drug candidate that inhibits the IDO pathway. Indoximod was tested in a Phase I study in combination with docetaxel and in a Phase IB/II study in combination with dendritic cell cancer vaccine. In both studies, data indicated that indoximod was well tolerated when combined with these anti-cancer agents. [Press release from NewLink Genetics Corporation discussing research presented at the American Society of Clinical Oncology (ASCO) 2013 Annual Meeting, Chicago] Press Release

Immunovaccine Shows Pronounced and Persistent T Cell Immune Responses in DPX-Survivac Cancer Vaccine Study

Immunovaccine Inc. (Immunovaccine) presented positive results from a Phase I clinical study of DPX-Survivac, one of the Company’s two clinical stage cancer vaccines. Immunovaccine highlighted study results that showed ovarian cancer patients treated with DPX-Survivac combined with low dose oral cyclophosphamide experienced pronounced and persistent T cell immune responses against survivin, a protein strongly associated with several tumor types. [Press release from Immunovaccine Inc. discussing research presented at the American Society of Clinical Oncology (ASCO) 2013 Annual Meeting, Chicago] Press Release

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SentoClone International AB Significantly Strengthens Its Global Patent Portfolio Covering its Clinical Stage Sentinel Node-Derived CD4 T-Cell Cancer Therapy
SentoClone International AB announced that it has been granted additional patents in Japan, the US and Europe further reinforcing the global protection of its proprietary SentoClone® technology, an active patient specific cellular immunotherapy against cancer based on the ex vivo cultivation and activation of CD4+ T-cells. [PR Newswire Association LLC] Press Release

ImmunoCellular Therapeutics Announces Recommendation of Data Monitoring Committee to Continue ICT-107 Phase II Trial Following Interim Analysis

ImmunoCellular Therapeutics, Ltd. announced that the Data Monitoring Committee has completed a pre-specified interim analysis of the ICT-107 Phase II clinical trial in patients with newly diagnosed glioblastoma and recommended that the company continue the trial to completion. The ICT-107 Phase II trial is a randomized, placebo-controlled, double-blind study of ICT-107, a 6-antigen dendritic cell vaccine targeting glioblastoma tumor and cancer stem cell antigens, as a potential treatment for patients with newly diagnosed glioblastoma. [ImmunoCellular Therapeutics, Ltd.] Press Release


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Therapeutic Goods Administration (Australia)


NEW NK2013 – 14th Meeting of the Society for Natural Immunity
September 18-22, 2013
Heidelberg, Germany

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NEW Director of Cell Processing Facility (S L Collins Associates, Inc.)

NEW PhD Studentship – Cancer and Chronic Inflammation (TU Dresden – Institute of Immunology)

NEW Postdoctoral Position – Immunological Modeling (Université catholique de Louvain (UCL))

Junior or Senior Group Leader – Immunology/Infection/Inflammation (Center of Pathophysiology of Toulouse Purpan)

Research Associates – Immune Response (NCSR Demokritos, Institute of Nuclear & Radiological Sciences & Technology, Energy & Safety)

Postdoctoral Position – Mechanistic Studies in Immune Responses (Medical University of Vienna)

Research Associate – NeuroOncology (University of Chicago – Department of Surgery)
Postdoctoral Researcher – Innate Immunity (Massachusetts General Hospital / Harvard Medical School)

Postdoctoral Fellowship – Tumor Immunology (Northwestern University – Robert H Lurie Comprehensive Cancer Center)

Postdoctoral Fellow – Immunological Pathways in Human Inflammatory Bowel Disease (Yale University – School of Medicine)

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