Immune Regulation News Volume 6.03 | Jan 31 2014

The Unfolded-Protein-Response Sensor IRE-1α Regulates the Function of CD8α⁺ Dendritic Cells
Investigators found that dendritic cells constitutively activated the unfolded protein response sensor IRE-1α and its target, the transcription factor XBP-1, in the absence of endoplasmic reticulum stress. [Nat Immunol] Abstract

The Transcription Factor IRF8 Activates Integrin-Mediated TGF-β Signaling and Promotes Neuroinflammation
By studying the role of interferon regulatory factor 8 (IRF8) in experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis, scientists found that Irf8^−/− mice are resistant to EAE. Expression of IRF8 in antigen-presenting cells such as macrophages, dendritic cells, and microglia, but not in T cells, facilitated disease onset and progression through multiple pathways. [Immunity] Abstract | Graphical Abstract

Oral Tolerance Can Be Established via Gap Junction Transfer of Fed Antigens from CX3CR1⁺ Macrophages to CD103⁺ Dendritic Cells
Researchers showed an unanticipated division of labor among antigen-presenting cells for the establishment of oral tolerance. Chemokine receptor CX3CR1⁺ macrophages were found to take up soluble fed antigens and quickly transfer them to CD103⁺ dendritic cells. [Immunity] Abstract | Graphical Abstract

In Vitro Membrane Reconstitution of the T-Cell Receptor Proximal Signaling Network
Scientists reconstituted the T-cell receptor phosphorylation signaling network using purified enzymes on liposomes, recapitulating the membrane environment in which they normally interact. [Nat Struct Mol Biol] Abstract

Intramuscular Therapeutic Vaccination Targeting HPV16 Induces T Cell Responses that Localize in Mucosal Lesions
The authors report marked immunologic changes in the target lesion microenvironment after intramuscular therapeutic vaccination targeting human papillomavirus serotype 16 (HPV16) E6/E7 antigens, in subjects with cervical intraepithelial neoplasias who had modest detectable responses in circulating T lymphocytes. [Sci Transl Med] Abstract | Press Release

PTPN2 Attenuates T-Cell Lymphopenia-Induced Proliferation
Researchers showed that protein tyrosine phosphatase N2 (PTPN2) is elevated in naive T cells leaving the thymus to restrict homoeostatic T-cell proliferation and prevent excess responses to self-antigens in the periphery. [Nat Commun] Abstract

Mst1/Mst2 Regulate Development and Function of Regulatory T Cells through Modulation of Foxo1/Foxo3 Stability in Autoimmune Disease
Investigators report that Mst1 regulates Foxp3 expression and regulatory T cell (Treg) development/function and inhibits autoimmunity through modulating Foxo1 and Foxo3 stability. They found that Mst1 deficiency impairs Foxp3 expression and Treg development and function in mice. [J Immunol] Abstract

LIM Domain Only-2 (LMO2) Induces T-Cell Leukemia by Two Distinct Pathways
The authors made transgenic mice with enforced expression of Lmo2 in T-cells by the CD2 promoter/enhancer. These transgenic mice developed highly penetrant T-ALL by two distinct patterns of gene expression: one in which there was concordant activation of Lyl1, Hhex, and Mycn or alternatively, with Notch1 target gene activation. [PLoS One] Full Article

The New Normal: Immunomodulatory Agents against Sepsis Immune Suppression
Recent studies from animal sepsis models and patient samples suggest that cytokines such as interleukin-7 (IL-7), IL-15, granulocyte macrophage colony-stimulating factor, as well as co-inhibitory molecule blockade, such as anti-programmed cell death receptor-1 and anti-B and T lymphocyte attenuator, may have utility in alleviating the clinical morbidity associated with sustained sepsis. This review discusses some of these novel immunomodulatory agents and evaluates their potential use as therapeutics. [Trends Mol Med] Abstract

Visit our reviews page to see a complete list of reviews in the immune regulation field.

Kiadis Pharma Initiates Collaboration for Personalized Immunotherapies Using ATIR™ with Technische Universität München within Munich Biotech Cluster
Kiadis Pharma B.V. announced that it has initiated a collaboration to identify and characterize leukemia-specific T-cells in Kiadis Pharma’s lead product ATIR™ that would be responsible for the Graft-versus-Leukemia effect of the T-cell immunotherapy product. [Kiadis Pharma B.V.] Press Release

Medigene Acquires Trianta Immunotherapies
Medigene AG has acquired Trianta Immunotherapies GmbH, a spin-off of the Helmholtz Zentrum München. Trianta is developing three complementary immunotherapy platforms with programs in clinical development to treat various tumor types. [Medigene AG] Press Release

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NEW Assistant Professor – Development of Novel Biologicals for Immune-based Disorders (Leiden Academic Centre For Drug Research)

Fellowship – Blockade of Immune Checkpoints to Increase the Efficacy of HER2 Vaccine (University of Turin)

Postdoctoral Position – Cell Signaling in the Immune System (Baylor Institute for Immunology Research)

Immunology Research Associate Position (Shanghai Jiaotong University School of Medicine)

Postdoctoral Position – Epigenetic Regulation of Interleukin-12 Family Members (Université Libre de Bruxelles)

Postdoctoral Position – Molecular/Cellular Immunology (National Institute of Allergy and Infectious Disease/National Institutes of Health)

PhD Position – Biology/Immunology (Saarland University)

Postdoctoral Position – Immunology/Cardiovascular Disease (Medical University of Innsbruck)

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

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