Immune Regulation News Volume 3.02 | Jan 21 2011

Scientists Find the “Master Switch” for Key Immune Cells in Inflammatory Diseases 
Scientists have identified a protein that acts as a “master switch” in certain white blood cells, determining whether they promote or inhibit inflammation. The study could help researchers look for new treatments for diseases such as rheumatoid arthritis that involve excessive inflammation. [Press release from Imperial College London discussing online prepublication in Nature Immunology]
 

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NIH Study in Mice Uncovers Pathway Critical for UV-Induced Melanoma
Scientists have made an unanticipated discovery in mice that interferon-gamma acts as a promoter for the deadly form of skin cancer known as melanoma. The results of this study suggest that interferon-gamma, which has been thought to contribute to an innate defense system against cancer, under some circumstances may promote melanoma and incite the development of tumors. [National Institutes of Health Press Release]

Mother’s Stem Cells Likely Key to Treating Genetic Disease before Birth
Through a series of mouse model experiments, the research team determined that a mother’s immune response prevents a fetus from accepting transplanted blood stem cells, and yet this response can be overcome simply by transplanting cells harvested from the mother herself. [Press release from the University of California, San Francisco discussing online prepublication in The Journal of Clinical Investigation]

Viral Protein Mimic Keeps Immune System Quiet
A team of researchers has shown for the first time that the Kaposi sarcoma virus has a decoy protein that impedes a key molecule involved in the human immune response. [Press release from ScienceDaily discussing online prepublication in Science]

Red Blood Cell Hormone Modulates the Immune System
New research reveals that a hormone best known for stimulating the production of red blood cells can modulate the immune response. The study finds that erythropoietin has contrasting influences on infectious and inflammatory diseases and may be useful in the design of new therapeutic strategies. [Press release from EurekAlert! discussing online prepublication in Immunity]

Study Maps Process Used by T Cells to Discriminate Pathogens
Researchers have for the first time mapped the complex choreography used by the immune system’s T cells to recognize pathogens while avoiding attacks on the body’s own cells. [Press release from Georgia Institute of Technology discussing online prepublication in Immunity]

CURRENT PUBLICATIONS (Ranked by Impact Factor of the Journal)

Reduction of Disulphide Bonds Unmasks Potent Antimicrobial Activity of Human Beta-Defensin 1
Defensins, characterized by three intramolecular disulphide-bridges, are key effector molecules of innate immunity that protect the host from infectious microbes and shape the composition of microbiota at mucosal surfaces. Herein researchers show that after reduction of disulphide-bridges human beta-defensin 1 becomes a potent antimicrobial peptide against the opportunistic pathogenic fungus Candida albicans and against anaerobic, Gram-positive commensals of Bifidobacterium and Lactobacillus species. [Nature]

Discovery of a Viral NLR Homolog that Inhibits the Inflammasome
The viral homolog subverts the function of cellular NLRs (nucleotide binding and oligomerization, leucine-rich repeat), which suggests that modulation of NLR-mediated innate immunity is important for the lifelong persistence of herpes viruses. [Science]

IRF5 Promotes Inflammatory Macrophage Polarization and TH1-TH17 Responses
Here researchers show that IRF5 expression in macrophages was reversibly induced by inflammatory stimuli and contributed to the plasticity of macrophage polarization. [Nat Immunol]

Erythropoietin Contrastingly Affects Bacterial Infection and Experimental Colitis by Inhibiting Nuclear Factor-B-Inducible Immune Pathways
Here, researchers show that erythropoietin (EPO) inhibits the induction of proinflammatory genes including tumor necrosis factor (TNF)-alpha and inducible nitric oxide synthase in activated macrophages, which is mechanistically attributable to blockage of nuclear factor (NF)-kappaB p65 activation by EPO. [Immunity]

Two-Stage Cooperative T Cell Receptor-Peptide Major Histocompatibility Complex-CD8 Trimolecular Interactions Amplify Antigen Discrimination
The T cell receptor and CD8 bind peptide-major histocompatibility complex glycoproteins to initiate adaptive immune responses, yet the trimolecular binding kinetics at the T cell membrane is unknown. By using a micropipette adhesion frequency assay, researchers show that this kinetics has two stages. [Immunity]

T Lymphocytes Negatively Regulate Lymph Node Lymphatic Vessel Formation
Lymph node lymphatic vessels (LNLVs) serve as a conduit to drain antigens from peripheral tissues to within the lymph nodes. LNLV density is known to be positively regulated by vascular endothelial growth factors secreted by B cells, macrophages, and dendritic cells (DCs). Here, researchers show that LNLV formation was negatively regulated by T cells. [Immunity]

Posttranscriptional Silencing of Effector Cytokine mRNA Underlies the Anergic Phenotype of Self-Reactive T Cells
Self-reactive T cell clones that escape negative selection are either deleted or rendered functionally unresponsive (anergic), thus preventing them from propagating host tissue damage. By using an in vivo model, researchers investigated molecular mechanisms for T cell tolerance, finding that despite a characteristic inability to generate effector cytokine proteins, self-reactive T cells express large amounts of cytokine mRNAs. [Immunity] 

Maternal T cells Limit Engraftment After In Utero Hematopoietic Cell Transplantation in Mice
Here, researchers have demonstrated that there is macrochimerism of maternal leukocytes in the blood of unmanipulated mouse fetuses, with substantial increases in T cell trafficking after in utero hematopoietic cell transplantation. [J Clin Invest]

Expression of p16INK4a Prevents Cancer and Promotes Aging in Lymphocytes
Here, using somatic, tissue-specific inactivation of the p16INK4a tumor suppressor in murine T- or B-lymphoid progenitors, researchers report that ablation of p16INK4a can either rescue aging or promote cancer in a lineage-specific manner. [Blood]

Two Distinct Auto-Regulatory Loops Operate at the PU.1 Locus in B cells and Myeloid Cells
Researchers previously identified an upstream regulatory cis-element (URE) whose targeted deletion in mice decreases PU.1 expression and causes leukemia. Researchers show here that the URE alone is insufficient to confer physiological PU.1 expression, but requires the cooperation with other, previously unidentified elements. [Blood]

 

Theraclone and Pfizer Enter into Infectious Disease and Cancer Antibody Discovery Collaboration
Theraclone Sciences, Inc., a therapeutic antibody discovery and development company, announced that they have entered into a multi-year research and development collaboration with Pfizer. [Theraclone Sciences, Inc. Press Release]

International Society for Cellular Therapy (ISCT) Launches Inaugural Cell Therapy Commercial Development Focus Group on Peripheral Vascular Disease
In keeping with its commitment to connect industry, regulatory experts, therapeutic societies and translational centers to advance emerging cellular therapies, ISCT announces its first commercial development focus group addressing Cell Therapies for Peripheral Vascular Disease (PVD). [PRNewswire]

Agennix AG Announces Longer-Term Mortality Data from Talactoferrin Phase II Trial in Severe Sepsis Presented at 40th Critical Care Congress
Agennix AG announced that new and more detailed data from a Phase II trial in severe sepsis with talactoferrin, an oral biologic therapy with immunomodulatory and antibacterial properties, were presented at the 40th Critical Care Congress of the Society of Critical Care Medicine in San Diego, California. [Agennix AG Press Release]
 

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