Immune Regulation News Volume 5.41 | Oct 25 2013

Itch Expression by Treg Cells Controls Th2 Inflammatory Responses
The authors showed that regulatory T (Treg) cell-specific ablation of the E3 ubiquitin ligase Itch in mice caused massive multiorgan lymphocyte infiltration and skin lesions, chronic T cell activation, and the development of severe antigen-induced airway inflammation. [J Clin Invest] Full Article | Press Release

Anti-CCR4 mAb Selectively Depletes Effector-Type Forkhead Box P3 (FoxP3)⁺CD4⁺ Regulatory T Cells, Evoking Antitumor Immune responses in Humans
Investigators showed that C-C chemokine receptor 4 (CCR4) was specifically expressed by a subset of terminally differentiated and most suppressive CD45RA^–FOXP3^hiCD4⁺ Treg cells, but not by CD45RA⁺FOXP3^loCD4⁺ naive regulatory T cells, in peripheral blood of healthy individuals and cancer patients. [Proc Natl Acad Sci USA] Abstract

PTEN Functions as a Melanoma Tumor Suppressor by Promoting Host Immune Response
Scientists studied the phenomena of immune evasion in malignant melanoma cells. They found that the tumor suppressor phosphatase and tensin homolog (PTEN) is an important regulator of the host immune response against melanoma cells. [Oncogene] Abstract

Microglial Activation Milieu Controls Regulatory T Cell Responses
Scientists showed that MHC class II⁺CD40^dimCD86^dimIL-10⁺ microglia are potent inducers of Ag-specific CD4⁺Foxp3⁺ regulatory T cells (Tregs) in vitro. Microglia differentially regulated MHC class II expression, costimulatory molecules, and IL-10 depending on the amount of IFN-γ challenge and Ag dose, promoting either effector T cell or Treg induction. [J Immunol] Abstract

Hepatocytes Contribute to Immune Regulation in the Liver by Activation of the Notch Signaling Pathway in T Cells
The authors showed that hepatocytes, particularly those from regenerating livers of Con A-pretreated mice, induced a regulatory phenotype in naive CD4⁺ T cells in vitro. Using reporter mice, they observed that these T regulatory cells released substantial amounts of IL-10, produced IFN-γ, failed to express Foxp3, but suppressed proliferation of responder T cells upon restimulation with anti-CD3 mAb. [J Immunol] Abstract

Selective Inhibition of Spleen Tyrosine Kinase (SYK) with a Novel Orally Bioavailable Small Molecule Inhibitor, RO9021, Impinges on Various Innate and Adaptive Immune Responses: Implications for SYK Inhibitors in Autoimmune Disease Therapy
A novel ATP-competitive inhibitor of SYK, 6-[(1R,2S)-2-Amino-cyclohexylamino]-4-(5,6-dimethyl-pyridin-2-ylamino)-pyridazine-3-carboxylic acid amide, designated RO9021, with an adequate kinase selectivity profile and oral bioavailability, was developed. In addition to suppression of B cell receptor signaling in human peripheral blood mononuclear cells and whole blood, FcγR signaling in human monocytes, and FcϵR signaling in human mast cells, RO9021 blocked osteoclastogenesis from mouse bone marrow macrophages in vitro. [Arthritis Res Ther] Full Article

CD4⁺CD62L⁺ Central Memory T Cells Can Be Converted to Foxp3⁺ T Cells
Researchers investigated the induction of Foxp3⁺ T cells from various CD4⁺ T-cell subsets in human peripheral blood. Though naive CD4⁺ T cells were readily converted to Foxp3⁺ T cells with TGF-β and IL-2 treatment in vitro, such Foxp3⁺ T cells did not express the memory marker CD45RO as do Foxp3⁺ T cells induced in the peripheral blood of Hepatitis B Virus patients. [PLoS One] Full Article

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Immunomedics Develops Dendritic-Cell Vaccine Technology for Lymphomas and Leukemias
Immunomedics, Inc. announced the issuance of U.S. patent no. 8,562,988 to its majority-owned subsidiary, IBCPharmaceuticals, Inc. for “Novel Strategies for Improved Cancer Vaccines.” [Immunomedics, Inc.]
Press Release

Adaptive Biotechnologies Receives Critical Intellectual Property for Next Generation Immunosequencing Field
Adaptive Biotechnologies Corporation announced that the company has obtained a Notice of Allowance in U.S. Patent Application Serial No. 12/794,507, titled “Method of Measuring Adaptive Immunity,” exclusively licensed by Adaptive Biotechnologies from the Fred Hutchinson Cancer Research Center. [Adaptive Biotechnologies Corporation] Press Release

Key Antibody Patent Granted in Japan
Cellmid Limited advises that the Japanese Patent Office granted Cellmid’s patent application JP 2007-544236 “Method for Treatment or Prevention of Diseases Associated with a Functional Disorder of Regulatory T Cells”. [Cellmid Limited] Press Release

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Postdoctoral Position – Lymphocyte Motility (INSERM)

Postdoctoral Research Fellow – Immunotherapy (Washington University School of Medicine)

Senior Principal Scientist – Immunology (Johnson & Johnson)

Postdoctoral Fellow – Ripk1 in Innate Immune Responses and Necroptosis (University of Massachusetts Medical School)

PhD Position – T-Lymphocyte Antigen Recognition (Medical University of Vienna)

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

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

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

Research Associate/Scientist – Antibodies Group (STEMCELL Technologies Inc.)

Scientist – Particle Chemistry (STEMCELL Technologies Inc.)

Research Associate – Particle Chemistry (STEMCELL Technologies Inc.)

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