Volume 5.41 | Oct 25

Immune Regulation News 5.41 October 25, 2013
Pulmonary Cell News
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Specification of Type 2 Innate Lymphocytes by the Transcriptional Determinant Gfi1
Researchers explored whether Gfi1 acts as a shared transcriptional determinant in type 2 innate lymphoid (ILC2) cells. Gfi1 promoted the development of ILC2 cells and controlled their responsiveness during infection with Nippostrongylus brasiliensis and protease allergen-induced lung inflammation. [Nat Immunol] Abstract
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Bee Venom Phospholipase A2 Induces a Primary Type 2 Response that Is Dependent on the Receptor ST2 and Confers Protective Immunity
Scientists examined how bee venom phospholipase A2 (PLA2) is sensed by the innate immune system and induces a type 2 immune response in mice. They found that bee venom PLA2 induced a T helper type 2 cell-type response and group 2 innate lymphoid cell activation via the enzymatic cleavage of membrane phospholipids and release of interleukin-33. [Immunity] Abstract

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 CD45RAFOXP3hiCD4+ Treg cells, but not by CD45RA+FOXP3loCD4+ 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+CD40dimCD86dimIL-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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DAMPs Activating Innate and Adaptive Immune Responses in COPD
As damage-associated molecular patterns (DAMPs) can attract and activate immune cells upon binding to pattern recognition receptors, the authors propose that their release may contribute to neutrophilic airway inflammation. They discuss the novel role of DAMPs in chronic obstructive pulmonary disease (COPD) pathogenesis. [Mucosal Immunol] Abstract

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PharmaCell Announces Agreement to Be – The European Contract Manufacturing Organization for Dendreon
PharmaCell announced that it has entered into an agreement with Dendreon Corporation to be the Contract Manufacturing Organization for the European commercial production of its recently approved cellular immunotherapy product Provenge® (autologous peripheral blood mononuclear cells activated with PAP-GM-CSF or sipuleucel-T) dispersion for infusion. [PharmaCell B.V.] Press Release

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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NEW Research Studentship – Imaging Membrane Lipid in Activating T Cells (King’s College London)

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)

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Scientist – Particle Chemistry (STEMCELL Technologies Inc.)

Research Associate – Particle Chemistry (STEMCELL Technologies Inc.)

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