Immune Regulation News Volume 5.16 | May 3 2013

The MicroRNA miR-155 Controls CD8⁺ T Cell Responses by Regulating Interferon Signaling
Scientists found upregulation of expression of the microRNA miR-155 in primary effector and effector memory CD8⁺ T cells, but low miR-155 expression in naive and central memory cells. Antiviral CD8⁺ T cell responses and viral clearance were impaired in miR-155-deficient mice, and this defect was intrinsic to CD8⁺ T cells, as miR-155-deficient CD8⁺ T cells mounted greatly diminished primary and memory responses. [Nat Immunol] Abstract

Mast Cell Maturation Is Driven via a Group III Phospholipase A₂-Prostaglandin D_2-DP1 Receptor Paracrine Axis
PLA2G3 secreted from mast cells were coupled with fibroblastic lipocalin-type PGD₂ synthase (L-PGDS) to provide PGD₂, which facilitates mast-cell maturation via PGD2 receptor DP1. Mice lacking PLA2G3, L-PGDS or DP1, mast cell-deficient mice reconstituted with PLA2G3-null or DP1-null mast cells, or mast cells cultured with L-PGDS-ablated fibroblasts exhibited impaired maturation and anaphylaxis of mast cells. [Nat Immunol] Abstract

Coexpression of CD49b and LAG-3 Identifies Human and Mouse T Regulatory Type 1 Cells
By gene expression profiling of human CD4⁺ type 1 T regulatory (Tr1) cell clones, the authors identified the surface markers CD49b and lymphocyte activation gene 3 (LAG-3) as being stably and selectively coexpressed on mouse and human Tr1 cells. [Nat Med] Abstract | Press Release

A Combination of Fluorescent NFAT and H2B Sensors Uncovers Dynamics of T Cell Activation in Real Time during Central Nervous System Autoimmunity
Investigators combined fluorescently labeled nuclear factor of activated T cells (NFAT) with histone protein H2B to create a broadly applicable molecular sensor for intravital imaging of T cell activation. [Nat Med] Abstract

CD40 Ligation Reverses T Cell Tolerance in Acute Myeloid Leukemia
A murine acute myeloid leukemia (AML) model was used to investigate antigen-specific T cell responses against AML cells inoculated i.v. versus s.c. Robust antigen-specific T cell responses were generated against AML cells after s.c., but not i.v., inoculation. [J Clin Invest] Full Article

Metallothioneins Negatively Regulate IL-27-Induced Type 1 Regulatory T-Cell Differentiation
Scientists showed that IL-27 induces metallothioneins (MTs) that in turn prevent type 1 regulatory T (Tr1) cell development. MT expression leads to the reduction of STAT1 and STAT3 phosphorylation under Tr1 differentiation condition, resulting in impaired IL-10 production. [Proc Natl Acad Sci USA] Abstract

The Lack of Maturation of Ebola Virus-Infected Dendritic Cells Results from the Cooperative Effect of At Least Two Viral Domains
Researchers investigated the contribution of Ebola virus proteins in modulating dendritic cell maturation by generating recombinant viruses expressing enhanced green fluorescent protein and carrying mutations affecting several potentially immunomodulating domains. [J Virol] Abstract | Press Release

Attenuated Natural Killer (NK) Cell Activation through NKp80 Is Due to an Anomalous Hemi-Immunoreceptor-Tyrosine-Based Activation Motif (hemITAM) with Impaired Syk Kinase Recruitment Capacity
The authors molecularly dissected the NKp80 hemITAM and demonstrated that two non-consenus amino acids, in particular arginine 6, critically impair both hemITAM phosphorylation and Syk recruitment. Impaired Syk recruitment results in a substantial attenuation of cytotoxic responses upon NKp80 ligation. [J Biol Chem] Abstract | Full Article

Proteinase-Activated Receptor-2 Modulates Human Macrophage Differentiation and Effector Function
Proteinase-activated receptor-2 (PAR-2) expression and activation was investigated on granulocyte macrophage and macrophage macrophages. In both macrophages, the PAR-2-activating peptide, SLIGKV, increased PAR-2 expression and regulated TNF-a and IL-10 secretion in a manner similar to LPS. [Innate Immun] Abstract

IL-6 Activated Integrated BATF/IRF4 Functions in Lymphocytes Are T-bet-Independent and Reversed by Subcutaneous Immunotherapy
Scientists found an inverse correlation between T-bet and Il-6 mRNA expression in asthmatic children. Moreover, experimental subcutaneous immunotherapy in T-bet^(-/-)mice inhibited IL-6, IL-21R and lung T_H17 cells in a setting of asthma. [Sci Rep] Full Article

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Beyond Oxidative Stress: An Immunologist’s Guide to Reactive Oxygen Species
Reactive oxygen species (ROS) react preferentially with certain atoms to modulate functions ranging from cell homeostasis to cell death. Cellular actions include promotion or suppression of inflammation, immunity and carcinogenesis. ROS chemistry and their pleiotropy make them difficult to localize, to quantify and to manipulate – challenges scientists must overcome to translate ROS biology into medical advances. [Nat Rev Immunol] Abstract

The Th17 Pathway as a Therapeutic Target in Rheumatoid Arthritis and Other Autoimmune and Inflammatory Disorders
The authors provide a clear overview of current knowledge on Th17 cell regulation and the main Th17 effector cytokines in relation to interleukin (IL)-17-mediated conditions, as well as on recent IL-17-related drug developments. [BioDrugs] Abstract

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Lupus Research Institute Tops $170 Million for Novel Research in Lupus
The Lupus Research Institute (LRI) announced a new $170 million milestone – delivering unprecedented novel research funding and unprecedented research results – changing the lives of lupus patients. A new analysis of completed LRI Novel Research grants demonstrates an 84 percent success rate as scientists prove cutting-edge hypotheses, publish results and win extended federal funding to advance original discoveries to clinical development. [Lupus Research Institute] Press Release

King of Sweden Presents Crafoord Award to Feinstein Institute Arthritis Researcher
Peter K. Gregersen, MD, a scientist at The Feinstein Institute for Medical Research was awarded the prestigious Crafoord Prize for his genetic research in the area of rheumatoid arthritis. [Feinstein Institute for Medical Research] Press Release

ImmusanT’s Epitope-Specific Immunotherapy for Celiac Disease Informs the Potential of Vaccines against Other Autoimmune Diseases
ImmusanT and its research partners are utilizing their expertise in celiac disease as a model to increase understanding of antigen-specific immunotherapy for autoimmune diseases. [ImmusanT, Inc.] Press Release

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May 15-18, 2013
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