Volume 5.32 | Aug 23

Immune Regulation News 5.32 August 23, 2013
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Inhibition of p300 Impairs Foxp3+ T Regulatory Cell Function and Promotes Antitumor Immunity
The authors report that conditional deletion or pharmacologic inhibition of one histone/protein acetyltransferases, p300, in Forkhead box P3 (Foxp3)+ T regulatory (Treg) cells increased T cell receptor-induced apoptosis in Treg cells, impaired Treg cell suppressive function and peripheral Treg cell induction, and limited tumor growth in immunocompetent but not in immunodeficient mice. [Nat Med]
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Rapid Effector Function of Memory CD8+ T Cells Requires an Immediate-Early Glycolytic Switch
Investigators showed that rapid interferon-γ production of effector memory CD8+ T cells, activated through stimulation mediated by the T cell antigen receptor and the costimulatory receptor CD28 or through cognate interactions, was linked to increased glycolytic flux. [Nat Immunol] Abstract

The Ubiquitin Ligase Stub1 Negatively Modulates Regulatory T Cell Suppressive Activity by Promoting Degradation of the Transcription Factor Foxp3
Researchers demonstrated that stress signals elicited by proinflammatory cytokines and lipopolysaccharides lead to the degradation of Foxp3 through the action of the E3 ubiquitin ligase Stub1. Stub1 interacted with Foxp3 to promote its K48-linked polyubiquitination in an Hsp70-dependent manner. [Immunity]
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Tristetraprolin Regulation of Interleukin 23 mRNA Stability Prevents a Spontaneous Inflammatory Disease
Scientists explored the role of the adenine and uridine-rich element-binding protein tristetraprolin in influencing mRNA stability of interleukin (IL)12p35, IL12/23p40, and IL23p19 subunits. [J Exp Med] Abstract

Lung Dendritic Cells Induce Migration of Protective T Cells to the Gastrointestinal Tract
To explore alternative pathways of cellular migration, scientists investigated the ability of dendritic cells (DCs) from mucosal and nonmucosal tissues to recruit lymphocytes to the gastrointestinal (GI) tract. Unexpectedly, they found that lung DCs, like CD103+ mesenteric lymph node DCs, up-regulate the gut-homing integrin α4β7 in vitro and in vivo, and induce T cell migration to the GI tract in vivo. [J Exp Med] Abstract

Differentiation and Functional Regulation of Human Fetal NK Cells
The authors showed that fetal natural killer (NK) cells differentiate early in utero and are highly responsive to cytokines and antibody-mediated stimulation but respond poorly to HLA class I-negative target cells. Strikingly, expression of killer-cell immunoglobulin-like receptors did not educate fetal NK cells but rendered them hyporesponsive to target cells lacking HLA class I. [J Clin Invest] Full Article

Specific Recruitment of γδ Regulatory T Cells in Human Breast Cancer
Investigators showed that IP-10 secreted by breast cancer cells attracted γδ regulatory T (Treg) cells. Using neutralizing antibodies against chemokines secreted by breast cancer cells, they found that IP-10 was the only functional chemokine that causes γδ Treg cells to migrate toward breast cancer cells. [Cancer Res] Abstract

Stress-Induced Recruitment of Bone Marrow-Derived Monocytes to the Brain Promotes Anxiety-Like Behavior
Scientists showed that repeated social defeat (RSD)-induced anxiety-like behavior corresponded with an exposure-dependent increase in circulating monocytes and brain macrophages. Moreover, RSD-induced anxiety-like behavior corresponded with brain region-dependent cytokine and chemokine responses involved with myeloid cell recruitment. [J Neurosci] Abstract | Press Release

CTLA4Ig Inhibits Effector T Cells through Regulatory T Cells and TGF-β
Researchers identified a novel, CD28-independent mechanism by which CTLA4Ig inhibits activated T cells. They showed that in vitro, CTLA4Ig synergizes with NO from bone marrow-derived macrophages to inhibit T cell proliferation. [J Immunol] Abstract
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Sterols and Oxysterols in Immune Cell Function
The authors review the literature on the biological functions of sterol intermediates and oxysterols, acting through transcription factors such as the liver X receptors, sterol regulatory element-binding proteins and the G protein-coupled receptor EBI2, in regulating the differentiation and population expansion of cells of the innate and adaptive immune systems, their responses to inflammatory mediators, their effects on the phagocytic functions of macrophages and their effects on antiviral activities and the migration of immune cells. [Nat Immunol] Abstract

Autophagy and Cellular Immune Responses
This review discusses the regulation of autophagy in the course of cellular immune responses and emphasize its impact on the immunogenicity of antigen-donor cells and on the activity of antigen-presenting cells and T lymphocytes. [Immunity] Abstract

B7 Family Checkpoint Regulators in Immune Regulation and Disease
The authors review recent understanding of B7 family members and their concerted regulation of the immune response to either self or foreign pathogens. They also discuss clinical developments in targeting these pathways in different disease settings, and introduce V-domain Ig suppressor of T cell activation as a putative therapeutic target. [Trends Immunol] Abstract

Visit our reviews page to see a complete list of reviews in the immune regulation field.
Duke Receives $1.3 Million for Immune Deficiency Research
Charles and Daneen Stiefel have given $1.3 million to support research at Duke Medicine that focuses on a group of diseases that compromise the immune system and increase the risk of infectious diseases and lymphoma. [Duke University] Press Release

NCBiotech Awards $3.58 Million in Quarter
Life science start-up companies, event sponsors, researchers and educators received $3.58 million in loans and grants from the North Carolina Biotechnology Center (NCBiotech) during the final quarter of the fiscal year. The awards, in 14 programs, went to successful applicants across the state to support life science entrepreneurship, technology commercialization and education. [North Carolina Biotechnology Center]
Press Release

Bio-Matrix Scientific Group Discusses Regen BioPharma’s Cancer Immunotherapy Program
Bio-Matrix Scientific Group Inc. (BMSN) provided an update on the cancer immunotherapy program currently under development by Regen BioPharma Inc., a wholly owned subsidiary of BMSN. [MarketWatch, Inc.]
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NEW 27th Annual Meeting European Macrophage & Dendritic Cell Society (EMDS) Meeting – Myeloid Cells: Microenvironment, Microorganisms & Metabolism
October 10-12, 2013
Erlangen, Germany

NEW The Role of Cytokines and Signaling in Inflammation
October 15, 2013
Bonn, Germany

Visit our events page to see a complete list of events in the immune regulation community.
NEW PhD Studentship – Regulatory Functions of B Cells (Deutsches Rheuma-Forschungszentrum Berlin)

NEW Postdoctoral Position – Identification of Novel Components of the Nlrp10 Pathway and their Effects on Dendritic Cell Mediated Immune Function

Research Technologist – Human Pluripotent Stem Cell Products (STEMCELL Technologies Inc.)

Research Scientist – Immune System Signaling (University of Pennsylvania)

Tenure-Track Position – Cell Biologist (McGill University)

Postdoctoral Scientist – Regulatory Activities of B Cells in Infectious and Autoimmune Diseases (Deutsches Rheuma-Forschungszentrum Berlin)

Postdoctoral Position – Innate Immune Signaling in the Developing Intestine (University of Connecticut Health Center)

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)

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

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

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