Immune Regulation News Volume 4.18 | May 18 2012

The Ubiquitin Ligase XIAP Recruits Linear Ubiquitin Chain Assembly Complex for NOD2 Signaling in Inflammation and Innate Immunity
Researchers demonstrated that the RING domain of X-linked Inhibitor of Apoptosis (XIAP) is essential for nucleotide-binding and oligomerization domain (NOD) 2 signaling and that XIAP contributes to exacerbation of inflammation-induced hepatitis in experimental mice. [Mol Cell] Abstract

Emergence of Distinct Multiarmed Immunoregulatory Antigen-Presenting Cells during Persistent Viral Infection
Scientists demonstrated that a distinct population of IL-10-expressing immunoregulatory antigen-presenting cells is amplified during chronic versus acute lymphocytic choriomeningitis virus infection and suppresses T cell responses. [Cell Host Microbe] Abstract

Mycobacterium Tuberculosis Activates the DNA-Dependent Cytosolic Surveillance Pathway within Macrophages
This work demonstrated that cytosolic sensing of mycobacterial DNA plays a key role in M. tuberculosis pathogenesis and likely contributes to the high type I IFN signature in tuberculosis. [Cell Host Microbe] Abstract

Deleterious Mutations in LRBA Are Associated with a Syndrome of Immune Deficiency and Autoimmunity
Researchers concluded that mutations in lipopolysaccharide responsive beige-like anchor protein (LRBA) cause an immune deficiency characterized by defects in B cell activation and autophagy and by susceptibility to apoptosis, all of which are associated with a clinical phenotype of hypogammaglobulinemia and autoimmunity. [Am J Hum Genet] Abstract

Canonical Autophagy Dependent on the Class III Phosphoinositide-3 Kinase Vps34 Is Required for Naïve T-Cell Homeostasis
Scientists report that Vps34 is required for the maintenance of naïve T cells, acting in a cell-intrinsic manner. T-cell-specific deletion of the gene encoding Vps34 resulted in reduced stability of Vps15 and Beclin-1 and impaired autophagy in T cells. [Proc Natl Acad Sci USA] Abstract

Alterations in RNA Processing during Immune-Mediated Programmed Cell Death
During immune-mediated death, death-inducing granzyme (Gzm) proteases concentrate in the nucleus of cells targeted for immune elimination, suggesting that nuclear processes are important targets. In this study, researchers used differential 2D proteomics of GzmA-treated nuclei to identify potential GzmA substrates. [Proc Natl Acad Sci USA] Abstract

cIAP1 and cIAP2 Limit Macrophage Necroptosis by Inhibiting Rip1 and Rip3 Activation
Researchers determined that cellular inhibitor of apoptosis proteins (cIAPs) have an important role in limiting programmed necrosis of macrophages. [Cell Death Differ] Abstract

Human B-Cell Ontogeny in Humanized NOD/SCID γc^null Mice Generates a Diverse yet Auto/Poly- and HIV-1-Reactive Antibody Repertoire
Single human B cells were sorted from bone marrow and periphery of humanized NOD/SCID γc^null mice at eight to ten months post engraftment with human cord blood-derived CD34⁺ stem cells. Human IG variable heavy (V_H) and kappa (V_κ) genes were amplified, cognate V_H-V_κ gene-pairs assembled as single-chain variable fragment-Fc antibodies and functional studies were performed. [Genes Immun] Abstract

In Vivo Immunoregulatory Properties of the Novel Mitochondria-Targeted Antioxidant SkQ1
Researchers investigated immunomodulatory properties of SkQ1 and demonstrated that treatment of mice with SkQ1 led to a decrease in percentage of CD8⁺ T cells but not of CD4⁺ T cells. [Mol Immunol] Abstract

World’s First Approved Stem Cell Drug; Osiris Receives Marketing Clearance from Health Canada for Prochymal
Osiris Therapeutics Inc. announced that it has received market authorization from Health Canada to market its stem cell therapy Prochymal^® (remestemcel-L), for the treatment of acute graft-vs-host disease in children. [Osiris Therapeutics, Inc.] Press Release

Bristol-Myers Squibb and Tsinghua University Enter Strategic Partnership
Under the agreement, Bristol-Myers Squibb will fund research efforts at Tsinghua University’s School of Life Sciences to identify and validate novel targets in oncology and immunoscience. [Bristol-Myers Squibb] Press Release

Intellect Neurosciences Expands Its Immunotherapy Pipeline with New Technology Platforms Targeting Pathogenic Protein Aggregates Focused on Huntington’s and Parkinson’s Diseases
Intellect Neurosciences, Inc. announced it has filed three new patent applications with the United States Patent and Trademark Office, which expand the Company’s immunotherapy pipeline. [Intellect Neurosciences, Inc.] Press Release

A Global Standard for Peer Review
After winning the strong backing of the White House, Subra Suresh convened a meeting of 47 leaders of research funding agencies from 44 countries. At the conclusion of closed-door sessions, the group will issue the first-ever global statement on the principles of merit review. [National Science Foundation, United States] Press Release

National Institutes of Health (United States)

Food and Drug Administration (United States)

Center for Biologics Evaluation and Research (United States)

European Medicines Agency (European Union)

Medicines and Healthcare Products Regulatory Agency (United Kingdom)

Therapeutic Goods Administration (Australia)

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