Volume 5.30 | Aug 9

Immune Regulation News 5.30 August 9, 2013
Pulmonary Cell News
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Mechanism Offers Promising New Approach for Harnessing the Immune System to Fight Cancer
Investigators identified a mechanism that boosts the ability of regulatory T cells to cause problems by blocking an effective anti-tumor immune response. Blocking this mechanism led to the elimination or dramatic reduction of melanoma by the immune system in mice, without causing the autoimmune and inflammatory problems often associated with current cancer-treatment efforts that target immune regulators. [Press release from St. Jude Children’s Research Hospital discussing online prepublication in Nature]
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Orchestrated Intron Retention Regulates Normal Granulocyte Differentiation
The authors’ bioinformatic analyses of transcriptomic and proteomic data of normal white blood cell differentiation reveal intron retention (IR) as a physiological mechanism of gene expression control. IR regulates the expression of 86 functionally related genes, including those that determine the nuclear shape that is unique to granulocytes. [Cell] Abstract | Graphical Abstract

Notch2-Dependent Classical Dendritic Cells Orchestrate Intestinal Immunity to Attaching-and-Effacing Bacterial Pathogens
Scientists used genetic techniques to deplete mice of specific subsets of classical dendritic cells (cDCs) and analyzed immunity to the attaching-and-effacing pathogen Citrobacter rodentium. They found that the signaling receptor Notch2 controlled the terminal stage of cDC differentiation. [Nat Immunol] Abstract

Nck-Mediated Recruitment of BCAP to the B Cell Antigen Receptor Regulates the PI(3)K-Akt Pathway in B Cells
Investigators found that Nck also controlled the phosphatidylinositol-3-OH kinase (PI(3)K)-kinase Akt pathway by recruiting the adaptor BCAP after activation of B cells. [Nat Immunol] Abstract

An Interleukin-17-Mediated Paracrine Network Promotes Tumor Resistance to Anti-Angiogenic Therapy
Researchers found that tumor-infiltrating T helper type 17 cells and interleukin-17 induced the expression of granulocyte colony-stimulating factor through nuclear factor κB and extracellular-related kinase signaling, leading to immature myeloid-cell mobilization and recruitment into the tumor microenvironment. [Nat Med] Abstract | Press Release

Type III TGF-β Receptor Downregulation Generates an Immunotolerant Tumor Microenvironment
Using murine models of breast cancer and melanoma, the authors elucidated a tumor immunoevasion mechanism whereby loss of tumor-expressed Type III TGF-β receptor/shed extracellular domain enhanced TGF-β signaling within locoregional DC populations and upregulated both the immunoregulatory enzyme indoleamine 2,3-dioxygenase in plasmacytoid DCs and the CCL22 chemokine in myeloid DCs. [J Clin Invest] Full Article | Press Release

Autonomic Dysreflexia Causes Chronic Immune Suppression after Spinal Cord Injury
Experimental activation of spinal sympathetic reflexes in spinal cord injury mice (e.g., via colorectal distension) elicits autonomic dysreflexia and exacerbates immune suppression via a mechanism that involves aberrant accumulation of norepinephrine and glucocorticoids. [J Neurosci] Abstract | Press Release

Multistage T Cell-Dendritic Cell Interactions Control Optimal CD4 T Cell Activation through the ADAP-Src Kinase-Associated Phosphoprotein of 55 kDa- Signaling Module
Using two-photon microscopy, scientists demonstrated that, in the absence of adhesion and degranulation promoting adapter protein (ADAP), CD4 T cells make fewer early-stage stable contacts with Ag-laden dendritic cells, and the interactions are characterized by brief repetitive contacts. [J Immunol] Abstract

Serine Protease Inhibitor 6 Plays a Critical Role in Protecting Murine Granzyme B-Producing Regulatory T Cells
The authors showed for the first time that both induced regulatory T cells (Tregs) and natural Tregs increase their intracellular expression of granzyme-B and its endogenous inhibitor, serine protease inhibitor 6 upon activation. [J Immunol] Abstract

Regulatory T Cells Prevent Th2 Immune Responses and Pulmonary Eosinophilia during RSV Infection in Mice
Investigators used the Foxp3DTR mice (that allow specific conditional depletion of Foxp3+ T cells) to investigate the functional effects of regulatory T cells during A2 strain respiratory syncytial virus (RSV) infection. [J Virol] Abstract

Inhibition of the Differentiation of Monocyte-Derived Dendritic Cells by Human Gingival Fibroblasts
Researchers investigated whether gingival fibroblasts can modulate the differentiation and/or maturation of monocyte-derived dendritic cells and analyzed soluble factors that may be involved in this immune modulation. [PLoS One] Full Article
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MicroRNA-Mediated Regulation of T Helper Cell Differentiation and Plasticity
The authors discuss recent advances and emerging ideas about how microRNAs – small endogenously expressed oligonucleotides that modulate gene expression – are involved in the regulatory networks that determine CD4+ T helper cell fate decisions and that regulate their effector functions. [Nat Rev Immunol] Abstract

Visit our reviews page to see a complete list of reviews in the immune regulation field.
Researchers Discover Leukemia’s Role in Inhibiting Immune Cell Development
University of California San Francisco’s Emmanuelle Passegué, PhD recently led a study in which researchers discovered how leukemia, a blood cancer, can gain a stronghold in bone marrow and inhibit the development of normal immune cells. [University of California San Francisco] Press Release

Arisaph Pharmaceuticals Awarded Phase I STTR Grant To Develop Small Molecule Immune Modulators
Arisaph Pharmaceuticals, Inc. announced that it has been awarded a Phase I Small Business Technology Transfer (STTR) award from the National Cancer Institute of the National Institutes of Health. The Phase I award supports the research and development of Arisaph’s small molecule immune modulators to stimulate tumor immunity following treatment with BRAF inhibitors in cancer. [PR Newswire Association LLC]
Press Release

Kite Pharma Appoints Leading Cancer Immunotherapy Experts to Its Scientific Advisory Board
Kite Pharma Inc. announced the appointment of three leading experts in the areas of immunotherapy, chimeric antigen receptor technology, and gene therapy to its Scientific Advisory Board. [PR Newswire Association LLC] Press Release

Stellar Biotechnologies Acquires Exclusive, Worldwide License to Clostridium difficile Immunotherapy Technology
Stellar Biotechnologies, Inc. announced that the Company has acquired the exclusive, worldwide license to patented technology for the development of human immunotherapies against Clostridium difficile infection from the University of Guelph. [Stellar Biotechnologies, Inc.] Press Release

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NEW Immunogenicity Summit 2013
November 11-13, 2013
Washington, United States

Visit our events page to see a complete list of events in the immune regulation community.
NEW Research Scientist – Immune System Signaling (University of Pennsylvania)

Tenure-Track Position – Cell Biologist (McGill University)

Postdoctoral Scientist – Regulatory Activities of B Cells in Infectious and Autoimmune Diseases (Deutsches Rheuma-Forschungszentrum Berlin)

Postdoctoral Position – Innate Immune Signaling in the Developing Intestine (University of Connecticut Health Center)

Postdoctoral Fellowship – Immune Regulation and Regulatory T Cells in Inflammation (University of Oslo – Centre for Immune Regulation)

Postdoctoral Fellowship – Immunology (Johns Hopkins University School of Medicine)

PhD Position – MMP-9 Domain Structure Involvement in Immunomodulation (KU Leuven)

PhD Research Position – Molecular and Cellular Mechanisms of Immune Tolerance and Autoimmunity (Weizmann Institute of Science)

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

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

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

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