Volume 5.27 | Jul 19

Immune Regulation News 5.27 July 19, 2013
Pulmonary Cell News
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A Secret to Making Macrophages
Biologists have worked out the details of a mechanism that leads undifferentiated blood stem cells to become macrophages- immune cells that attack bacteria and other foreign pathogens. The process involves an unexpected cycle in which cell division slows, leading to an increased accumulation of a particular regulatory protein that in turn slows cell division further. [Press release from the California Institute of Technology discussing online prepublication in Science] Press Release | Abstract | Video
A New System for High-Throughput Cell Isolation Directly from Whole Blood
PUBLICATIONS (Ranked by impact factor of the journal)
Antiapoptotic Mcl-1 Is Critical for the Survival and Niche-Filling Capacity of Foxp3+ Regulatory T Cells
The authors report that peripheral Foxp3+ regulatory T cells markedly alter their proliferative and apoptotic rates to rapidly restore numerical deficit through an interleukin 2-dependent and costimulation-dependent process. [Nat Immunol] Abstract | Press Release

Intravenous Immunoglobulin Expands Regulatory T Cells via Induction of Cyclooxygenase-2-Dependent Prostaglandin E2 in Human Dendritic Cells
As CD4+CD25+FoxP3+ regulatory T cells (Tregs) expansion in the periphery requires signaling by antigen presenting cells such as dendritic cells (DCs) and that intravenous immunoglobulin (IVIg) has been demonstrated to modulate DC functions, investigators hypothesized that IVIg induces distinct signaling events in DCs that subsequently mediate Treg expansion. They demonstrated that IVIg expands Tregs via induction of cyclooxygenase-2-dependent prostaglandin E2 in human DC. [Blood] Abstract

Transient B Cell Depletion Combined with Apoptotic Donor Splenocytes Induces Xeno-Specific T and B Cell Tolerance to Islet Xenografts
Peritransplant infusion of apoptotic donor splenocytes cross-linked with ethylene carbodiimide (ECDI-SPs) has been demonstrated to effectively induce allogeneic donor-specific tolerance. Researchers aimed to determine the effectiveness and additional requirements for tolerance induction for xenogeneic islet transplantation using donor ECDI-SPs. In a rat-to-mouse xenogeneic islet transplant model, they showed that rat ECDI-SPs alone significantly prolonged islet xenograft survival, but failed to induce tolerance. [Diabetes]
| Press Release

Modulation of CD8+ T Cell Responses to AAV Vectors with IgG-Derived MHC Class II Epitopes
Using MHC class II epitopes initially identified within human IgG, named Tregitopes, researchers showed that it is possible to modulate CD8+ T cell responses to several viral antigens in vitro. They showed that incubation of peripheral blood mononuclear cells with these epitopes triggers proliferation of CD4+CD25+FoxP3+ T cells that suppress killing of target cells loaded with MHC class I antigens in an antigen-specific fashion, through a mechanism that seems to require cell-to-cell contact. [Mol Ther] Abstract

Membrane-Type 6 Matrix Metalloproteinase Regulates the Activation-Induced Downmodulation of CD16 in Human Primary NK Cells
Scientists identified membrane-type 6 (MT6) matrix metalloproteinase (MMP) (also known as MMP25) as a proteinase responsible for CD16 downmodulation. IL-2-induced upregulation of MT6/MMP25 cell-surface expression correlates with CD16 downmodulation. [J Immunol] Abstract

Tumor-Infiltrating Regulatory T Cells Inhibit Endogenous Cytotoxic T Cell Responses to Lung Adenocarcinoma
The authors examined immune complexity of human nonsmall cell lung cancers (NSCLC) as well as NSCLC developing in CC10-TAg transgenic mice, and revealed that CD4+ T lymphocytes represent the dominant population of CD45+ immune cells, and, relative to normal lung tissue, CD4+Foxp3+ regulatory T cells were significantly increased as a proportion of total CD4+ cells. [J Immunol] Abstract

Human Cytomegalovirus Viral IL-10 Polarizes Monocytes Towards a Deactivated M2c Phenotype to Repress Host Immune Responses
Investigators identified a novel role for viral interluekin (IL)-10 in driving M2c polarization which may limit virus clearance by restricting pro-inflammatory and CD4+ T cell responses at sites of infection. [J Virol] Abstract

KLF4 Modulates Expression of IL-6 in Dendritic Cells via Both Promoter Activation and Epigenetic Modification
Researchers showed a novel role for the zinc finger transcription factor Kruppel like factor 4 (KLF4) in the modulation of the inflammatory immune response via its regulation of IL-6. They analyzed the role of KLF4 in the production of IL-6 by dendritic cells. [J Biol Chem] Abstract | Full Article

Innate Immune-Directed NF-κB Signaling Requires Site-Specific NEMO Ubiquitination
Scientists knock in a NF-κB essential modulator (NEMO) allele in which two major inflammatory agonist-induced ubiquitination sites cannot be ubiquitinated. They showed that mice with a nonubiquitinatable NEMO allele display embryonic lethality. Heterozygous females develop inflammatory skin lesions, decreased B cell numbers, and hypercellular spleens. [Cell Rep] Abstract | Graphical Abstract | Full Article

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Isolate Mouse Cells In As Little As 15 Minutes
CTLA-4 and Autoimmunity: New Insights into the Dual Regulator of Tolerance
Multiple single-nucleotide polymorphisms have been located to human Ctla-4 gene, and their association with autoimmune disease is still a matter of controversy. Despite the promising results of abatacept or CTLA-4-Ig in rheumatoid arthritis and murine lupus nephritis, more clinical randomized trials and standardization of outcomes are needed to prove its efficacy and safety in human lupus nephritis. [Autoimmun Rev] Abstract

Invariant Natural Killer T Cells in Adipose Tissue: Novel Regulators of Immune-Mediated Metabolic Disease
The authors summarize recent work on invariant natural killer T (iNKT) cells in immune regulation, with an emphasis on adipose tissue-resident iNKT cells, and identify the potential mechanisms by which adipocytes can mediate iNKT cell activity. [Cell Mol Life Sci] Abstract

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Immunomedics Constructs New Humanized Antibody for B-cell Mediated Cancer and Autoimmune Diseases
Immunomedics, Inc. reported the issuance of U.S. Patent 8,486,395 with expiration on August 2, 2024. The new patent covers additional claims for the patent family, “Anti-CD19 Antibodies.” The allowed claims protect our new, proprietary humanized hA19 antibody and cover its use for the treatment of B-cell lymphoma, chronic lymphocytic leukemia or acute lymphocytic leukemia. [Immunomedics, Inc.] Press Release

Researcher Finds Way to Convert Blood Cells into Autoimmune Disease Treatment
Cells from one’s own blood could be converted into a treatment for autoimmune diseases, like rheumatoid arthritis and Crohn’s disease, based on the discovery of a Purdue University researcher. Chang Kim, a professor of comparative pathobiology, has created a way to direct the differentiation of T-cells, a white blood cell that is a key player in the body’s immune system. The method uses naïve T-cells, immature cells from which all T-cells develop, and induces them to become suppressive T-cells that block the development of painful inflammation associated with autoimmune diseases. [Purdue University] Press Release

ARIAD Names Sarah J. Schlesinger, M.D. of Rockefeller University to Its Board of Directors
ARIAD Pharmaceuticals, Inc. announced the appointment of Sarah J. Schlesinger, M.D., senior attending physician and associate professor of clinical investigation in the Laboratory of Cellular Physiology and Immunology at The Rockefeller University, to its Board of Directors. Dr. Schlesinger is a prominent clinical investigator and immunologist who has spent more than 20 years working in the field of cellular immunity, including as clinical director of the laboratory led by the late Ralph M. Steinman, M.D., 2011 Nobel Laureate in Physiology or Medicine. [ARIAD Pharmaceuticals, Inc.] Press Release

NeoStem Advances Autoimmune Platform through UCSF Collaboration
NeoStem, Inc. announced that the Company has executed agreements with the University of California, San Francisco (UCSF) and the laboratories of Jeffrey Bluestone, PhD, and Qizhi Tang, PhD, to collaborate on the development of human regulatory T cells for the treatment of type 1 diabetes, steroid resistant asthma, and organ transplant rejection. [NeoStem, Inc.] Press Release

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NEW Postdoctoral Fellowship – Immune Regulation and Regulatory T Cells in Inflammation (University of Oslo – Centre for Immune Regulation)

Postdoctoral Position – Immunology (Mount Sinai School of Medicine)

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

Postdoctoral Fellowship – Immunology (Johns Hopkins University School of Medicine)

PhD Position – MMP-9 Domain Structure Involvement in Immunomodulation (KU Leuven)

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

Postdoctoral Scientists – Immune Cell Biology (Medical Research Council – National Institute for Medical Research)

Director of Cell Processing Facility (S L Collins Associates, Inc.)

Junior or Senior Group Leader – Immunology/Infection/Inflammation (Center of Pathophysiology of Toulouse Purpan)

Postdoctoral Position – Mechanistic Studies in Immune Responses (Medical University of Vienna)

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