Immune Regulation News Volume 9.00 | Jan 6 2017

TOP STORY

Increased Peripheral CD4⁺ Regulatory T Cells Persist after Successful Direct-Acting Antiviral Treatment of Chronic Hepatitis C

Researchers analyzed regulatory T cells before, at end of therapy (EOT), 12 and 24 weeks and long-term after EOT in 26 genotype-1-infected patients successfully treated with sofosbuvir plus IFN/ribavirin and IFN-free directly acting antivirals regimens. Frequency, phenotype and suppressor function of peripheral Foxp3⁺CD25⁺CD4⁺ T cells were studied by multi-color flow cytometry and co-culture inhibition assays. [J Hepatol] Abstract

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Cocapture of Cognate and Bystander Antigens Can Activate Autoreactive B Cells

Using flow cytometry and live and fixed cell microscopy, scientists showed that myelin oligodendrocyte glycoprotein (MOG)-specific B cells take up large amounts of MOG from cell membranes. Uptake of the antigen from the membrane leads to a strong activation of the capturing B cell. [Proc Natl Acad Sci USA] Abstract | Press Release | Video

CD73 Regulates Anti-Inflammatory Signaling between Apoptotic Cells and Endotoxin-Conditioned Tissue Macrophages

Investigators used low-dose endotoxin conditioning (LEC) of mouse resident peritoneal macrophages to model the effects of suboptimal, antecedent TLR activation on macrophage inflammatory responses to apoptotic cells. Compared with unconditioned macrophages (MФ), LEC-MФ showed a significant enhancement of apoptotic cell-driven suppression of many inflammatory cytokines. [Cell Death Differ] Abstract

A Negative Feedback Loop of ICER and NF-κB Regulates TLR Signaling in Innate Immune Responses

The NF-κB pathway has important roles in innate immune responses and its regulation is critical to maintain immune homeostasis. The authors report a newly discovered feedback mechanism for the regulation of this pathway by TLR ligands in macrophages. [Cell Death Differ] Abstract

c-FLIP Expression in Foxp3-Expressing Cells Is Essential for Survival of Regulatory T Cells and Prevention of Autoimmunity

The authors showed that, compared to conventional T cells, regulatory T cells have a high apoptosis rate ex vivo correlating with low c-FLIP expression. [Cell Rep] Full Article | Graphical Abstract

Intrinsic 4-1BB Signals Are Indispensable for the Establishment of an Influenza-Specific Tissue-Resident Memory CD8 T-Cell Population in the Lung

Scientists showed that intranasal administration of 4-1BBL along with influenza nucleoprotein in a replication-defective adenovirus vector to influenza pre-immune mice induces a remarkably stable circulating effector memory CD8 T-cell population characterized by higher IL-7Rα expression than control-boosted T cells, as well as a substantial lung parenchymal CD69⁺ CD8 memory T cells population, including both CD103⁺ and CD103⁻ cells. [Mucosal Immunol] Abstract

Neutrophilic NLRP3 Inflammasome-Dependent IL-1β Secretion Regulates the γδT17 Cell Response in Respiratory Bacterial Infections

Researchers highlighted an unexpected key role for neutrophils as accessory cells in innate interleukin (IL)-17A production by lung resident Vγ6Vδ1⁺ T cells via nucleotide-binding oligomerization domain receptor, pyrin-containing 3 (NLRP3) inflammasome-dependent IL-1β secretion. [Mucosal Immunol] Abstract

Mesenchymal Stem Cells Ameliorate B-Cell-Mediated Immune Responses and Increase IL-10-Expressing Regulatory B Cells in an EBI3-Dependent Manner

The authors investigated the effect of human palatine tonsil-derived mesenchymal stem cells (T-MSCs) on estradiol (E2)-induced B-cell responses in vivo and in vitro. Transplantation of T-MSC into E2-treated mice alleviated B-cell-mediated immune responses and increased the population of IL-10-producing B_reg cells. [Cell Mol Immunol] Abstract

Cathepsin S Inhibition Changes Regulatory T-Cell Activity in Regulating Bladder Cancer and Immune Cell Proliferation and Apoptosis

In vitro, inhibitor-treated regulatory T cells (Tregs) showed lower proliferation and higher apoptosis than saline-treated Tregs when cells were exposed to MB49. In contrast, both types of Tregs showed no difference in proliferation when they were co-cultured with normal splenocytes. [Mol Immunol] Abstract

Ginsenoside Rb2 Enhances the Anti-Inflammatory Effect of ω-3 Fatty Acid in LPS-Stimulated RAW264.7 Macrophages by Upregulating GPR120 Expression

Scientists investigated whether ginsenoside Rb2 (Rb2), which exhibited regulatory activities in glucose and lipid metabolism, affected GPR120 expression in lipopolysaccharide (LPS)-activated mouse macrophage RAW264.7 cells, and examined the contribution of GPR120 activation to reducing the LPS-induced inflammatory response. [Acta Pharmacol Sin] Abstract

Heme Oxygenase-1-Expressing Dendritic Cells Promote Foxp3⁺ Regulatory T Cell Differentiation and Induce Less Severe Airway Inflammation in Murine Models

Scientists demonstrated that heme oxygenase-1 (HO-1)-expressing bone marrow-derived dendritic cells (DCs) displayed tolerogenic phenotypes, including their resistance to lipopolysaccharide-induced maturation, high level expression of IL-10, and low T-cell stimulatory activity. In addition, HO-1-expressing DCs were able to induce antigen-specific Foxp3⁺ regulatory T cells differentiation in vitro and in vivo. [PLoS One] Full Article

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FOXP3-Positive Regulatory T Cells and Kidney Allograft Tolerance

Normal immune homeostasis is achieved by several mechanisms, and prominent among them is immunoregulation. Although several types of regulatory lymphocyte populations have been described, CD4 T cells expressing the FOXP3 transcription factor are the best understood. [Am J Kidney Dis] Abstract

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AbCellera Announces Multi-Target Research Collaboration with Pfizer

AbCellera Biologics, Inc. announced a new therapeutic antibody discovery collaboration with Pfizer Inc. AbCellera will apply its proprietary monoclonal antibody screening platform to attempt to discover function-modulating antibodies against undisclosed membrane protein targets. [AbCellera Biologics, Inc.] Press Release

Seattle Genetics Initiates Phase I Trial of SGN-CD352A for Patients with Relapsed or Refractory Multiple Myeloma

Seattle Genetics, Inc. announced enrollment of the first patient in a multicenter Phase I clinical trial of SGN-CD352A for patients with relapsed or refractory multiple myeloma. SGN-CD352A is an investigational CD352-targeted antibody-drug conjugate (ADC) utilizing Seattle Genetics’ proprietary ADC technology, an engineered cysteine antibody stably linked to a highly potent cytotoxic agent called a pyrrolobenzodiazepine dimer. [Seattle Genetics, Inc.] Press Release

Rgenix Announces Treatment of First Patient in Phase I Trial of RGX-104, its Lead Immuno-Oncology Therapeutic

Rgenix, Inc. announced treatment of the first patient with its lead candidate RGX-104 in a Phase I a/b study. [Rgenix, Inc. (Business Wire, Inc.)] Press Release

US Scientists Fear New Restrictions on Fetal-Tissue Research

House Republicans conclude that tissue from aborted fetuses is of limited value for research and seek to reduce funding. [Nature News] Editorial

Argentina’s Researchers Occupy Science Ministry

Hundreds of young researchers occupied Argentina’s science ministry in Buenos Aires last month, angry at budget cuts that they say have denied them permanent jobs at the country’s National Scientific and Technical Research Council. The occupation was the most extreme action yet by Argentinian scientists after months of protests at last year’s budget, the first under President Mauricio Macri. And the occupation seems to have paid off, in part: many of those involved have been offered extensions to their fellowships. [Nature News] Editorial

Scientists in Germany, Peru and Taiwan to Lose Access to Elsevier Journals

Thousands of scientists in Germany, Peru and Taiwan are preparing for a new year without online access to journals from the Dutch publishing giant Elsevier. Contract negotiations in both Germany and Taiwan broke down in December, while Peru’s government has cut off funding for a licence. [Nature News] Editorial

NEW Keystone Symposium: Injury, Inflammation and Fibrosis
March 26-30, 2017
Snowbird, United States

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NEW Senior Scientist (Immatics Biotechnologies GmbH)

NEW Postdoctoral Position – Vascular Control of Immune Cell Infiltration and Metastasis (German Cancer Research Center)

Research Technologist – Cell Separation (STEMCELL Technologies Inc.)

Senior Scientist – Immunology (Immusoft Corporation)

Postdoctoral Position – Pre-Clinical In Vivo Studies and Immunology (German Cancer Research Center)

Postdoctoral Research Fellow – Cell Death and Immunity (Fred Hutchinson Cancer Research Center)

Postdoctoral Research Fellow – Immune Regeneration (Fred Hutchinson Cancer Research Center)

Postdoctoral Position – Immunology of HIV-1 and Cancer (University of Alabama at Birmingham)

Postdoctoral Position – Visceral Pain and Neuro-Immune Interaction (KU Leuven)

Assistant Associate or Full Member – Cancer Immunology (Fred Hutchinson Cancer Research Center)

Postdoctoral Fellow – Molecular Immunology (University of California, San Diego)

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