Volume 4.32 | Aug 24

Immune Regulation News 4.32 August 24, 2012
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Endogenous Antigen Tunes the Responsiveness of Naive B Cells but Not T Cells
Scientists demonstrated that B cells encounter antigen during development in the spleen, and that this antigen exposure, in turn, tunes the responsiveness of B-cell antigen receptor signalling in B cells at least partly by downmodulating expression of surface IgM but not IgD BCRs, and by modifying basal calcium levels. By contrast, no analogous process occurs in naive mature T cells. [Nature] Abstract

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T Cells Become Licensed in the Lung to Enter the Central Nervous System
In the autoimmune disease multiple sclerosis, myelin-reactive T-cell blasts are thought to transgress the blood-brain barrier (BBB) and create a pro-inflammatory environment in the central nervous system (CNS), thereby making possible a second autoimmune attack that starts from the leptomeningeal vessels and progresses into the parenchyma. Using a Lewis rat model of experimental autoimmune encephalomyelitis, researchers showed that contrary to the expectations of this concept, T-cell blasts do not efficiently enter the CNS and are not required to prepare the BBB for immune-cell recruitment. [Nature] Abstract

Acute Gastrointestinal Infection Induces Long-Lived Microbiota-Specific T Cell Responses
The authors showed that during a gastrointestinal infection, tolerance to commensals is lost and microbiota-specific T cells are activated and differentiate to inflammatory effector cells. Furthermore, these T cells go on to form memory cells that are phenotypically and functionally consistent with pathogen-specific T cells. [Science] Abstract

Interleukin-22 Protects Intestinal Stem Cells from Immune-Mediated Tissue Damage and Regulates Sensitivity to Graft versus Host Disease
Researchers demonstrated that deficiency of recipient-derived interleukin (IL)-22 increased acute graft versus host disease (GvHD) tissue damage and mortality, that intestinal stem cells were eliminated during GvHD, and that intestinal stem cells as well as their downstream progenitors expressed the IL-22 receptor. [Immunity] Abstract

A Broad Range of Self-Reactivity Drives Thymic Regulatory T Cell Selection to Limit Responses to Self
Researchers analyzed a panel of T cell receptors (TCRs) with a broad range of reactivity to ovalbumin (OVA323-339) in the rat insulin promoter-mOVA self-antigen model for their ability to trigger thymic self-tolerance mechanisms. Thymic regulatory T cell generation in vivo was directly correlated with in vitro TCR reactivity to OVA-peptide in a broad 1,000-fold range. [Immunity] Abstract

Nucleic Acid-Containing Amyloid Fibrils Potently Induce Type I Interferon and Stimulate Systemic Autoimmunity
The authors report that nucleic acid-containing amyloid fibrils can potently activate plasmacytoid dendritic cells (pDCs) and enable type I interferon (INF) production in response to self-DNA, self-RNA, and dead cell debris. pDCs can take up DNA-containing amyloid fibrils, which are retained in the early endosomes to activate TLR9, leading to high IFNα/β production. [Proc Natl Acad Sci USA] Abstract

The Proinflammatory Myeloid Cell Receptor TREM-1 Controls Kupffer Cell Activation and Development of Hepatocellular Carcinoma
Researchers report causal evidence that TREM-1 is a pivotal determinant of Kupffer cell activation in liver carcinogenesis, deepening mechanistic insights into how chronic inflammation underpins the development and progression of liver cancer. [Cancer Res] Abstract | Press Release

Plexin-B2 and Plexin-D1 in Dendritic Cells: Expression and IL-12/IL-23p40 Production
This is the first report to show an association between Plexin-B2 and Plexin-D1 with the negative regulation of IL-12/IL-23p40 in dendritic cells (DCs). This work also showed the presence of Plexin-B2 and Plexin-D1 on mouse DC subpopulations, and indicated that these two proteins play a role in IL-12/IL-23p40 production that is likely to impact the immune response. [PLoS One] Full Article

Improving Dendritic Cell Vaccine Immunogenicity by Silencing PD-1 Ligands Using siRNA-Lipid Nanoparticles Combined with Antigen mRNA Electroporation
Researchers explored the generation of a clinical-grade applicable dendritic cell (DC) vaccine with improved immunogenic potential by combining PD-1 ligand siRNA and target antigen mRNA delivery. They demonstrated that PD-L1 and PD-L2 siRNA delivery using DLin-KC2-DMA-containing lipid nanoparticles mediated efficient and specific knockdown of PD-L expression on human monocyte-derived DC. [Cancer Immunol Immunother] Abstract | Press Release

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The Anatomical and Cellular Basis of Immune Surveillance in the Central Nervous System
This review describes the anatomical and cellular basis of immune surveillance in the central nervous system, and explains how this shapes the unique immunology of these tissues. [Nat Rev Immunol] Abstract

FOXO Transcription Factors Throughout T Cell Biology
The authors propose that the forkhead box O (FOXO) transcription factor family provides connections between physical well-being and the form and magnitude of an immune response. They present a case that FOXO transcription factors guide T cell differentiation and function in a context-driven manner, and might provide a link between metabolism and immunity. [Nat Rev Immunol] Abstract

The Role of the T Follicular Helper Cells in Allergic Disease
This review examines the evidence that these cells are responsible for regulating IgE class switching and the relationship between T follicular helper cells and T helper 2 effector cells. [Cell Mol Immunol] Abstract


Kineta Announces Regulatory Clearance to Initiate a Phase I Clinical Trial for ShK-186
Kineta, Inc. announced it has received regulatory clearance in the Netherlands to initiate a first-in-human trial of ShK-186, an autoimmune drug candidate that specifically inhibits the Kv1.3 potassium ion channel. [Business Wire] Press Release

ImmunoCellular Therapeutics Appoints John S. Yu, MD, as Interim Chief Executive Officer
ImmunoCellular Therapeutics, Ltd. announced that the Board of Directors has appointed John S. Yu, MD, as Interim Chief Executive Officer and President, and has accepted the resignation of Manish Singh, PhD, effective immediately, from the CEO, President, and Board positions. Dr. Yu will continue to serve as Chief Scientific Officer and Chairman of the Board. [ImmunoCellular Therapeutics, Ltd.] Press Release

The Kenneth Rainin Foundation Announces $1,000,000 in Grants Awarded for Innovative IBD Research
The Kenneth Rainin Foundation announced the recipients of its 2012 Innovator Awards and its 2012 Breakthrough Awards for Inflammatory Bowel Disease (IBD) research. Innovator Award recipients will each receive a $100,000 grant to support their respective innovative research projects. [PR Newswire]
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Research Technologist – Media Development (STEMCELL Technologies, Inc.)

Research Technologist – Research and Development (STEMCELL Technologies, Inc.)

Scientific Communications & Publishing Coordinator (STEMCELL Technologies, Inc.)

Quality Control Operations Coordinator (STEMCELL Technologies, Inc.)

Scientist – Mesenchymal Cell Research (STEMCELL Technologies, Inc.)

Postdoctoral Position – Immunology (San Raffaele Scientific Institute)

Postdoctoral Research Position (University Lille 2 France)

Postdoctoral Position – Immunology (Louisiana State University)

Postdoctoral Position – Immunology (San Raffaele Scientific Institute)

Research Technician I – Immunology (La Jolla Institute for Allergy and Immunology)

Postdoctoral Positions – Immunity and Inflammation (CNRS & University of Toulouse, France)

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