Volume 5.33 | Aug 30

Immune Regulation News 5.33 August 30, 2013
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Pivotal Roles of cGAS-cGAMP Signaling in Antiviral Defense and Immune Adjuvant Effects
Investigators showed that cells from cyclic GMP(cGAMP)-AMP synthase (cGAS)-deficient mice, including fibroblasts, macrophages and dendritic cells, failed to produce type I interferons and other cytokines in response to DNA transfection or DNA virus infection. [Science] Abstract | Press Release
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Bacteria Activate Sensory Neurons that Modulate Pain and Inflammation
Researchers demonstrated that bacteria directly activate nociceptors, and that the immune response mediated through TLR2, MyD88, T cells, B cells, and neutrophils and monocytes is not necessary for Staphylococcus aureus-induced pain in mice. [Nature] Abstract | Press Release

Stabilization of the Transcription Factor Foxp3 by the Deubiquitinase USP7 Increases Treg-Cell-Suppressive Capacity
Scientists demonstrated that the expression of the transcription factor Foxp3 can be regulated through the polyubiquitination of multiple lysine residues, resulting in proteasome-mediated degradation. Expression of the deubiquitinase USP7 was found to be upregulated and active in regulatory T (Treg) cells, being associated with Foxp3 in the nucleus. [Immunity] Abstract | Graphical Abstract

Up-Regulation of PD-L1, IDO, and Tregs in the Melanoma Tumor Microenvironment Is Driven by CD8+ T Cells
Although evidence for an active immune response, including infiltration with CD8+ T cells, can be found in a subset of patients, those tumors are nonetheless not immunologically rejected. The authors showed that it is the subset of T cell-inflamed tumors that showed high expression of three defined immunosuppressive mechanisms: indoleamine-2,3-dioxygenase (IDO), PD-L1/B7-H1, and FoxP3+ regulatory T cells (Tregs), suggesting that these inhibitory pathways might serve as negative feedback mechanisms that followed, rather than preceded, CD8+ T cell infiltration. [Sci Trans Med] Abstract

Complement Modulates the Cutaneous Microbiome and Inflammatory Milieu
Scientists revealed an interactive role for complement in cutaneous host-microbiome interactions. Inhibiting signaling of the complement component C5a receptor altered the composition and diversity of the skin microbiota as revealed by deep sequencing of the bacterial 16S rRNA gene. [Proc Natl Acad Sci USA] Abstract | Press Release

Expression of the Immune Regulator Tripartite-Motif 21 Is Controlled by IFN Regulatory Factors
The authors demonstrated that IFNs induce Tripartite-motif 21 (Trim21) expression in immune cells via IFN regulatory factors and that IFN-α and IFN-β are the most potent inducers of Trim21. [J Immunol] Abstract

Mbd2 Promotes Foxp3 Demethylation and T-Regulatory Cell Function
Conserved CpG dinucleotides in the regulatory T (Treg)-specific demethylated region upstream of Foxp3 are demethylated only in stable, thymic-derived Foxp3+ Tregs. Since methyl-binding domain (Mbd) proteins recruit histone-modifying and chromatin-remodeling complexes to methylated sites, the authors tested whether targeting of Mbd2 might promote demethylation of Foxp3 and thereby promote Treg numbers or function. [Mol Cell Biol] Abstract

PARP-1 Controls Immunosuppressive Function of Regulatory T Cells by Destabilizing Foxp3
Investigators showed that Poly (ADP-ribose) polymerase-1 (PARP-1) regulates the suppressive function of CD4+CD25+Foxp3+ regulatory T cells. [PLoS One] Full Article

Extensive Cooperation of Immune Master Regulators IRF3 and NFκB in RNA Pol II Recruitment and Pause Release in Human Innate Antiviral Transcription
To investigate RNA polymerase II (Pol II) recruitment and elongation in the human antiviral gene regulatory network, a comprehensive genome-wide analysis was conducted during the initial phase of virus infection. Results reveal extensive integration of interferon regulatory factor 3 (IRF3) and nuclear factor κB (NFκB) with Pol II and associated machinery and implicate partners for antiviral transcription. [Cell Rep]
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Cyclic Dinucleotides and the Innate Immune Response
Cyclic dinucleotides (CDNs) have been previously recognized as important secondary signaling molecules in bacteria and, more recently, in mammalian cells. In the former case, they represent secondary messengers affecting numerous responses of the prokaryotic cell, whereas in the latter, they act as agonists of the innate immune response. Remarkable new discoveries have linked these two patterns of utilization of CDNs as secondary messengers and have revealed unexpected influences they likely had on shaping human genetic variation. [Cell] Full Article

Dendritic Cells and Other Innate Determinants of T Helper Cell Polarization
Recent studies have demonstrated that the innate immune system functions to direct the adaptive immune response, not only through antigen presentation but also by providing the key signals for the differentiation of naive CD4+ T cells into functionally distinct T helper cell subtypes. [Trends Immunol] Abstract

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New Project Investigates Immune System’s Role in Multiple Sclerosis
A $1.3 million grant from the National Institute of Neurological Disorders and Stroke could help Houston Methodist scientists better understand how the body’s own immune system drives multiple sclerosis. [Houston Methodist] Press Release

Opexa Announces Issuance of 50th Patent for T-Cell Immunotherapy Platform
Opexa Therapeutics, Inc. announced that several key patents have issued, further strengthening the Company’s proprietary technology for the development of patient-specific immunotherapies. [Opexa Therapeutics, Inc.] Press Release

Cellular Biomedicine Group Announces Completion of Patient Enrollment for Phase I Clinical Trial for Liver Cancer
Cellular Biomedicine Group announced that it has completed patient enrollment for its Phase I trial to evaluate the safety and preliminary efficacy of Tumor Stem Cell Specific Dendritic Cell therapy for hepatocellular carcinoma, the most common type of liver cancer. [Cellular Biomedicine Group] Press Release

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NEW PhD/Postdoctoral Positions – Quantitative T-cell Immunology (University of Leeds)

PhD Studentship – Regulatory Functions of B Cells (Deutsches Rheuma-Forschungszentrum Berlin)

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

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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)

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

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

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