Volume 5.06 | Feb 15

Immune Regulation News 5.06 February 15, 2013
     In this issue: Publications | Reviews | Science News | Industry News | Policy News | Events | Jobs
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TOP STORY
Phosphorylation of FOXP3 Controls Regulatory T Cell Function and Is Inhibited by Tumor Necrosis Factor α in Rheumatoid Arthritis
Scientists demonstrated that forkhead box P3 (FOXP3) transcriptional activity and, consequently, regulatory T cell suppressive function are regulated by phosphorylation at Ser418 in the C-terminal DNA-binding domain. [Nat Med] Abstract

Air-Liquid Interface Culture for Respiratory Research: Watch Q&A Video
PUBLICATIONS (Ranked by impact factor of the journal)

Mast Cell Interleukin-10 Drives Localized Tolerance in Chronic Bladder Infection
Investigators identified a broadly immunosuppressive transcriptional program specific to the bladder, but not the kidney, during infection of the urinary tract that is dependent on tissue-resident mast cells. This involves localized production of interleukin-10 and results in suppressed humoral and cell-mediated responses and bacterial persistence. [Immunity] Abstract | Graphical Abstract | Press Release

IL-21 Stimulated Human Plasmacytoid Dendritic Cells Secrete Granzyme B, which Impairs Their Capacity to Induce T Cell Proliferation
The authors demonstrated that Granzyme B induction was in part responsible for IL-21-mediated downmodulation of CD4+ T cell proliferation induced by Toll-like-receptor pre-activated plasmacytoid dendritic cells. [Blood] Abstract

Antidiabetogenic MHC Class II Promotes the Differentiation of MHC-Promiscuous Autoreactive T Cells into FOXP3+ Regulatory T Cells
Researchers showed that the antidiabetogenic MHC class II molecule I-Ab affords diabetes resistance by promoting the differentiation of MHC-promiscuous autoreactive CD4+ T cells into disease-suppressing natural regulatory T cells, in a β56-67-regulated manner. [Proc Natl Acad Sci USA] Abstract

Calcium Flashes Orchestrate the Wound Inflammatory Response through DUOX Activation and Hydrogen Peroxide Release
Scientists revealed that laser wounding of the Drosophila embryo epidermis triggers an instantaneous calcium flash, which travels as a wave via gap junctions several cell rows back from the wound edge. Blocking this calcium flash inhibits hydrogen peroxide release at the wound site and leads to a reduction in the number of immune cells migrating to the wound. [Curr Biol] Abstract | Press Release

Sustained Tumor Eradication after Induced Caspase-3 Activation and Synchronous Tumor Apoptosis Requires an Intact Host Immune Response
Although apoptosis is generally considered nonimmunogenic, recent evidence suggests that some anticancer therapies that induce apoptosis can elicit antitumor immune responses. The authors constructed a doxycycline-inducible, constitutively active caspase-3 (‘death switch’) in a murine tumor model to explore the impact of the host immune response to rapid, synchronous and substantial tumor cell apoptosis. [Cell Death Differ] Abstract

Asymptomatic Plasmodial Infection Is Associated with Increased TNFRII-Expressing Tregs and Suppressed Type 2 Immune Responses
In 80 schoolchildren residing in a malaria-endemic area of Flores Island, Indonesia, T-helper subsets, regulatory T-cell (Treg) frequencies, TNFRII expression on Treg and P. falciparum-infected red blood cell-induced cytokine responses were measured and asymptomatic infected subjects were compared to uninfected controls. [J Infect Dis] Abstract

The Requirement of Linker for Activation of T Cells in the Primary and Memory Responses of CD8 T Cells
To study the role of TCR-mediated signaling in CD8 T cells during the course of pathogen infection, investigators used an inducible mouse model to delete linker for activation of T cells in Ag-specific CD8 T cells at different stages of Listeria infection and analyzed the effect of deletion on T cell responses. [J Immunol] Abstract

Sialoadhesin Ligand Expression Identifies a Subset of CD4+Foxp3 T Cells with a Distinct Activation and Glycosylation Profile
Researchers examined the induction of Sn ligands (SnL) on all splenic CD4+ T cells following in vitro activation. Most CD4+ regulatory T cells strongly upregulated SnL, whereas only a small subset of ~20% CD4+Foxp3 T cells upregulated SnL. [J Immunol] Abstract

Galectin-9 Functionally Impairs Natural Killer (NK) Cells in Humans and Mice
Researchers found that galectin-9 ligation down-regulates multiple immune activating genes including eight involved in the NK cell-mediated cytotoxicity pathway, impairs lymphokine-activated killing, and decreases the proportion of IFN-γ producing NK cells that had been stimulated with IL-12/IL-15. [J Virol] Abstract

Partial Depletion of Regulatory T Cells Does Not Influence the Inflammation Caused by High Dose Hemi-Body Irradiation
The effects of partial depletion of regulatory T cells with an anti-CD25 antibody in conjunction with ionizing radiation on inflammation and tissue injury were analyzed in C57BL/6 mice. [PLoS One] Full Article


Learn more about the new smartphone app for human blood cell frequencies

REVIEWS

Intravenous Immunoglobulin Therapy: How Does IgG Modulate the Immune System?
The authors cover the recent insights into the molecular and cellular pathways that are involved in intravenous immunoglobulin (IVIG)-mediated immunosuppression, with a particular focus on IVIG as a therapy for IgG-dependent autoimmune diseases. [Nat Rev Immunol] Abstract

Activating Natural Cytotoxicity Receptors of Natural Killer Cells in Cancer and Infection
The natural cytotoxicity receptors (NCRs) NKp30, NKp44, and NKp46 are important mediators of natural killer (NK) cell cytotoxicity, which trigger an immune response on recognition of cognate cellular and viral ligands. Tumor and viral immune escape strategies targeting these receptor-ligand systems impair NK cell cytotoxicity and promote disease. Therefore, a molecular understanding of the function of the NCRs in immunosurveillance is instrumental to discovering novel access points to combat infections and cancer. [Trends Immunol] Abstract


Regulatory Functions of Innate-Like B Cells
The authors highlight the latest advances in the field of innate-like B cells and focuses on their regulatory functions. [Cell Mol Immunol] Abstract

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SCIENCE NEWS
AbbVie Announces First Long-Term, Patient-Reported Health Outcomes Data for Use of HUMIRA® (Adalimumab) in Patients with Pediatric Crohn’s Disease
AbbVie announced the first long-term, patient-reported health outcomes data from analyses of the Phase III IMAgINE-1 trial. The analyses assessed improvements in health-related quality of life measures for pediatric patients aged 6 to 17 years with severe active Crohn’s disease, taking HUMIRA, who had an inadequate response, were intolerant or had contraindications to conventional therapy, as well as the work productivity of their caregivers throughout the 52-week study. [Press release from AbbVie discussing research to be presented at the European Crohn’s and Colitis Organization (ECCO) 8th Annual Congress, Vienna]
Press Release
INDUSTRY NEWS

Ablynx’s Anti-IL-6R Nanobody, ALX-0061, Shows Excellent 24 Week Safety and Efficacy Results in a Phase II Clinical Trial in Rheumatoid Arthritis
Ablynx announced efficacy and safety data for its anti-IL-6R Nanobody, ALX-0061, at the 24 week final analysis of the Phase II part of a combined Phase I/II study in patients with moderately to severely active rheumatoid arthritis (RA) on a stable background of methotrexate. ALX-0061 targets the interleukin 6 (IL-6) pathway via its IL-6receptor (IL-6R), which plays a fundamental role in the inflammation process in RA. [Ablynx]
Press Release

Third Rock Ventures Launches Jounce Therapeutics with $47 Million Series A to Transform Cancer Treatment
Third Rock Ventures, LLC announced the formation of Jounce Therapeutics, Inc. with a $47 million Series A financing of the company. Jounce is focused on the discovery and development of first-in-class cancer immunotherapies designed to harness the patient’s immune system to seek out and attack cancerous cells and tumors. [Jounce Therapeutics, Inc.] Press Release

UB Ontologists Named to Major NIH Immunology Research Team

A team of University at Buffalo (UB) researchers have been selected by the National Institutes of Health (NIH) to support the collection, analysis and exchange of scientific data for scientists investigating immunology and immune-mediated diseases. [University at Buffalo] Press Release

POLICY NEWS

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)

EVENTS

NEW Keystone Symposia on Molecular and Cellular Biology: Immunopathology of Type 1 Diabetes
April 4-9, 2013
Whistler, Canada

Visit our events page to see a complete list of events in the immune regulation community.

JOB OPPORTUNITIES

Postdoctoral Fellow – Transcriptional Regulation in CD8 T Lymphocytes (Université Libre de Bruxelles – Institute for Medical Immunology)

Faculty Positions – Cancer Inflammation and Tolerance (Georgia Health Sciences University Cancer Center)

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


Postdoctoral Position – IL-17 and Inflammation Research (Hospices Civils de Lyon)

PhD Position – Mast Cells in HPV-Induced Skin Cancer (TU Dresden – Institute of Immunology)

PhD candidate – Immunoregulatory Properties of Stromal and Immune Cells (University of Saarland, Internal Medicine II)

Postdoctoral Position – NK/T Cells (The Ohio State University – Comprehensive Cancer Center)

Postdoctoral Position – Microbiota and Pro-Inflammatory Lymphoid Cells (Laboratory of Lymphoid Tissue Development, Institut Pasteur)

Research Specialist – Tolerance and Antirejection Techniques in Transplantation (University of Chicago)


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