Immune Regulation News Volume 3.08 | Mar 4 2011

Jekyll and Hyde: Cells’ Executioner Can Also Stave Off Death
An enzyme viewed as an executioner, because it can push cells to commit suicide, may actually short circuit a second form of cell death, researchers have discovered. [Press release from Emory University Woodruff Health Sciences Center discussing online prepublication in Nature]

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Protein’s Elusive Role in Embryo and Disease Development Unravelled
Scientists have determined that a single protein called FADD controls multiple cell death pathways, a discovery that could lead to better, more targeted autoimmune disease and cancer drugs. [Press release from ScienceDaily discussing online prepublication in Nature]

Scientists Tie Cell Cycle “Clock” To Childhood Cancers
Abnormal chromosomes have long been detected in children with leukemias and lymphomas, and now, research has linked such abnormalities with a molecular clock that controls the timing of a high-stakes genetic exchange inside dividing immune system cells. [Press release from Johns Hopkins University discussing online prepublication in Immunity]

New Cell Therapy A Promising Atherosclerosis Treatment
Researchers have shown in a new study on mice that cell therapy can be used to reverse the effect of ‘bad’ LDL cholesterol and reduce the inflammation that leads to atherosclerosis. [Press release from Karolinska Institutet discussing online prepublication in Circulation]

Research Opens Door to Vaccines That Can Circumvent Maternal Antibodies
New research that reveals how maternal antibodies block an immune response to the measles virus is a first step toward improving current childhood vaccination practices, scientists say. [Press release from Ohio State University discussing online prepublication in Blood]

NIH Scientists Unveil Characteristic of HIV Early in Transmission
Researchers at the have helped explain genetic differences that can distinguish some early-transmitting HIVs from forms of HIV isolated later in infection. The study also sheds light on CD4+ T cells, the primary immune cell targeted by HIV. [Press release from the National Institutes of Health (NIH) National Institute of Allergy and Infectious Diseases discussing online prepublication in PLoS Pathogens]

Cytheris Announces Results of Phase IIa Study Indicating that Recombinant Interleukin-7 (CYT107) Expands CD4 T-Cells in Gut Mucosa of Chronically HIV Infected Immunological Non-Responder Patients
Cytheris SA announced results of a multi-center Phase IIa study designed to investigate the potential of CYT107 therapy to reconstitute CD4 T-cells in chronically HIV-1 infected patients whose CD4 T-cell counts remained low despite treatment with anti-retroviral-therapies. [Press release from Cytheris SA discussing research presented at the 2011 Conference on Retroviruses and Opportunistic Infections]

New Vaccine Technology Protects Mice from Hepatitis C Virus
Researchers at the University of Copenhagen are now the first to succeed in developing a vaccine, which provides future hope for medical protection from hepatitis C. [University of Copenhagen Press Release]

Functional Complementation Between FADD and RIP1 in Embryos and Lymphocytes
Data demonstrate an unexpected cell-type-specific interplay between FADD and RIP1, which is critical for the regulation of apoptosis and necrosis during embryogenesis and lymphocyte function. [Nature]

RIP3 Mediates the Embryonic Lethality of Caspase-8-Deficient Mice
Caspase-8 (Casp8) contributes to homeostatic control in the adult immune system; however, RIP3 and Casp8 are together completely dispensable for mammalian development. [Nature]

The Kinase mTOR Regulates the Differentiation of Helper T Cells Through the Selective Activation of Signaling by mTORC1 and mTORC2
Here researchers demonstrate that differentiation into the T_H1 and T_H17 subsets of helper T cells was selectively regulated by signaling from mTOR complex 1 (mTORC1) that was dependent on the small GTPase Rheb. [Nat Immunol]

The Helminth Product ES-62 Protects Against Septic Shock via Toll-like Receptor 4–Dependent Autophagosomal Degradation of the Adaptor MyD88
Here researchers found that phagocytes from patients with sepsis had considerable upregulation of Toll-like receptor 4 (TLR4) and TLR2; however, shock-inducing inflammatory responses mediated by these TLRs were inhibited by ES-62, an immunomodulator secreted by the filarial nematode Acanthocheilonema viteae. [Nat Immunol]

Coupling of V(D)J Recombination to the Cell Cycle Suppresses Genomic Instability and Lymphoid Tumorigenesis
Scientists infer that cell cycle control of the V(D)J recombinase limits the potential genomic damage that could otherwise result from RAG-mediated DNA cleavage. [Immunity]

Immunotherapy with Tolerogenic Apolipoprotein B-100–Loaded Dendritic Cells Attenuates Atherosclerosis in Hypercholesterolemic Mice
Tolerogenic dendritic cells pulsed with apolipoprotein B100 reduced the autoimmune response against low-density lipoprotein and may represent a novel possibility for treatment or prevention of atherosclerosis. [Circulation]

Dectin-2 Mediates Th2 Immunity Through the Generation of Cysteinyl Leukotrienes
Using lentiviral knockdown of Dectin-2 in GM-CSF–cultured bone marrow cells (BMCs^GM-CSF) and adoptive transfer of Dermatophagoides farinae (Df)-pulsed BMCs^GM-CSF to sensitize naive mice, researchers now report that Dectin-2 is critical for the development of Df-elicited eosinophilic and neutrophilic pulmonary inflammation and Th2 cytokine generation in the lungs and restimulated lymph nodes. [J Exp Med]

Insights Into the Regulatory Mechanism Controlling the Inhibition of Vaccine-Induced Seroconversion by Maternal Antibodies
The data demonstrates that maternal antibodies inhibit B cell responses by interaction with the inhibitory/regulatory Fc(gamma)RIIB receptor and not through epitope masking. [Blood]

The Genotype of Early-Transmitting HIV gp120s Promotes Alpha₄Beta₇–Reactivity, Revealing Alpha₄Beta₇⁺/CD4⁺ T cells as Key Targets in Mucosal Transmission
Using primary alpha₄beta₇⁺/CD4⁺ T cells and a flow-cytometry based steady-state binding assay researchers show that the removal of transmission-associated N-linked glycosylation sites results in large increases in the specific reactivity of gp120 for integrin-alpha₄beta₇. [PLoS Pathogens]

IL-17+ Regulatory T Cells in the Microenvironments of Chronic Inflammation and Cancer
The biology of IL-17+Foxp3+CD4+ T cells remains poorly understood in humans. Researchers investigated their phenotype, cytokine profile, generation, and pathological relevance in patients with ulcerative colitis. [J Immunol]

Bayhill Therapeutics Announces the Successful Clearance of an IND for BHT-3034 for the Treatment of Myasthenia Gravis
Bayhill Therapeutics Inc, a clinical-stage biopharmaceutical company utilizing its proprietary BHT-DNA™ platform to develop novel and targeted autoimmune and immune-mediated disease treatments, announced the successful clearance of an IND with the US FDA for BHT-3034, a disease-modifying DNA plasmid vaccine immunotherapy for patients with the autoimmune neuromuscular junction disease myasthenia gravis. [FierceBiotech]

Sangamo BioSciences Announces Presentation of Positive Clinical Data From Novel ZFN Therapeutic Approach for the Treatment of HIV/AIDs at Conference for Retroviral and Opportunistic Infections
Sangamo BioSciences, Inc. announced the presentation of positive preliminary clinical data from its Phase I trial (SB-728-902). [Sangamo BioSciences, Inc. Press Release]

China Follows B.C.’s Lead on HIV/AIDS Treatment
The Chinese government has announced it will use a treatment strategy developed in B.C. to combat the spread of HIV and AIDS in China. [The Vancouver Sun]

Phase I/II Clinical Study of IFN(alpha)-Kinoid for Lupus Fully Enrolled
Neovacs, a biotech company focused on an active immunotherapy technology platform (Kinoids™) with applications in the treatment of autoimmune diseases, inflammatory diseases and cancer, announced that its IFN-K-001 clinical study has recruited all 28 patients called for by the study protocol and consistent with the Company’s development plan. [Neovacs Press Release]

Lycera Announces Research Collaboration with Merck to Discover, Develop and Commercialize Drugs for Autoimmune Diseases
Lycera Corporation announced that it has entered into an exclusive research collaboration with Merck to discover, develop and commercialize small molecules that target T-helper 17 cells, key mediators of inflammation. [Lycera Corporation Press Release]

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