Immune Regulation News Volume 6.15 | May 2 2014

Polarization of the Effects of Autoimmune and Neurodegenerative Risk Alleles in Leukocytes
To extend the understanding of the genetic basis of human immune function and dysfunction, researchers performed an expression quantitative trait locus study of purified CD4⁺ T cells and monocytes, representing adaptive and innate immunity, in a multi-ethnic cohort of 461 healthy individuals. [Science]
Abstract | Press Release

Interleukin-10 Receptor Signaling in Innate Immune Cells Regulates Mucosal Immune Tolerance and Anti-Inflammatory Macrophage Function
Intact interleukin-10 (IL-10) receptor signaling on effector and T regulatory cells are each independently required to maintain immune tolerance. Researchers showed that IL-10 sensing by innate immune cells, independent of its effects on T cells, was critical for regulating mucosal homeostasis. [Immunity]
Abstract | Graphical Abstract

Inflammatory T Cell Responses Rely on Amino Acid Transporter ASCT2 Facilitation of Glutamine Uptake and mTORC1 Kinase Activation
Researchers have shown that naive T cell activation is coupled with rapid glutamine uptake, which depended on the amino acid transporter ASCT2. ASCT2 deficiency impaired the induction of T helper 1 (Th1) and Th17 cells and attenuated inflammatory T cell responses in mouse models of immunity and autoimmunity. [Immunity] Abstract

PD-L1 Is a Novel Direct Target of HIF-1α, and Its Blockade under Hypoxia Enhanced MDSC-Mediated T Cell Activation
Investigators demonstrated that myeloid-derived suppressor cells (MDSCs) at the tumor site show a differential expression of programmed death ligand 1 (PD-L1) as compared with MDSCs from peripheral lymphoid organ (spleen). Hypoxia caused a rapid, dramatic, and selective up-regulation of PD-L1 on splenic MDSCs in tumor-bearing mice. This was not limited to MDSCs, as hypoxia also significantly increased the expression of PD-L1 on macrophages, dendritic cells, and tumor cells. [J Exp Med] Abstract

T Helper Cell IL-4 Drives Intestinal Th2 Priming to Oral Peanut Antigen, under the Control of OX40L and Independent of Innate-Like Lymphocytes
Investigators showed that interleukin-4 (IL-4)-dependent peanut allergic T helper type 2 (Th2) responses are completely intact in natural killer-like T-deficient, γδ T-deficient or innate lymphoid cell-deficient mice, including antigen-specific IgG1/IgE production, anaphylaxis, and cytokine production. [Mucosal Immunol] Abstract

Selective Antigen-Specific CD4⁺ T-Cell, but Not CD8⁺ T- or B-Cell, Tolerance Corrupts Cancer Immunotherapy
Researchers demonstrated that for some antigens self-tolerance reflects selective elimination of antigen-specific CD4⁺ T cells, but preservation of CD8⁺ T- and B-cell populations. In mice, antigen-specific CD4⁺ T-cell tolerance restricted CD8⁺ T- and B-cell responses targeting the endogenous self antigen guanylyl cyclase c in colorectal cancer. [Eur J Immunol] Abstract | Press Release

Phagocytosis of Apoptotic or Necrotic Cells Differentially Regulates the Transcriptional Expression of IL-12 Family Members in Dendritic Cells
Researchers investigated how uptake of dead cells affects the production and expression of different members of the IL-12 family by immature dendritic cells (DCs) or TolDCs. They showed that compared to regular immature DCs, TolDCs display elevated levels of PS-recognizing bridge molecule receptors αvβ5 and CD36, and have enhanced phagocytic abilities with accelerated uptake of apoptotic cells. [J Leukoc Biol] Abstract

Ubiquitous Points of Control Over Regulatory T Cells
The authors summarize and discuss several examples of ubiquitin-mediated control over multiple aspects of regulatory T cell biology including the generation, function and phenotypic fidelity of these cells. [J Mol Med] Abstract

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Medigene Receives New US Patent for TCR-Modified T Cell Immunotherapy
Medigene AG announced that the US Patent Office has issued patent No. 8,697,854 “High affinity T cell receptor and use thereof”, relating to T-cell receptors against the tumor associated antigen tyrosinase. [Medigene AG] Press Release

Innovative Research Effort Will Learn More about Rheumatoid Arthritis
Investigators at the University of Alabama at Birmingham have teamed with the Global Healthy Living Foundation’s arthritis support community CreakyJoints.org to launch a study which will incorporate electronic devices to capture important information on conditions such as rheumatoid arthritis from patients and physicians. [University of Alabama at Birmingham] Press Release

Scripps Florida Scientists Awarded Grant to Develop New Diagnostics for Cancer, Rheumatoid Arthritis, Colitis
Scientists from the Florida campus of The Scripps Research Institute have been awarded a $2.3 million grant from the National Institute of General Medical Sciences of the National Institutes of Health to develop new technology to diagnose cancer, rheumatoid arthritis and colitis. [The Scripps Research Institute] Press Release

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NEW Postdoctoral Associate/Research Scientist – Macrophage Biology (Massachusetts Institute of Technology – MIT)

NEW Research Technologist – hPSC (STEMCELL Technologies Inc.)

Postdoctoral Position – Intestinal Immunology (Biomedical Sciences Research Center “Alexander Fleming”)

Postdoctoral Position – Neuro-Immune Interactions (ICM Foundation – Brain and Spinal Cord Research Institute)

Postdoctoral Research Associate – Infection and Immunity (University College London)

Postdoctoral Associate – Immunology (Virginia Bioinformatics Institute at Virginia Tech)

Postdoctoral Position – Immunology (University of Pittsburgh)

Director of GMP/GLP Quality Operations (University of Pennsylvania, Perelman School of Medicine)

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

Research Associate – Cell Separation (STEMCELL Technologies Inc.)

Research Technologist – Pluripotent Stem Cells (STEMCELL Technologies Inc.)

Research Technologist – PSC Biology and Bioengineering (STEMCELL Technologies Inc.)

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