Volume 6.24 | Jul 4

Immune Regulation News 6.24 July 4, 2014
Immune Regulation News
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The Metabolic Checkpoint Kinase mTOR Is Essential for IL-15 Signaling during the Development and Activation of NK Cells
Researchers found that the metabolic checkpoint kinase mTOR was activated and boosted bioenergetic metabolism after exposure of natural killer (NK) cells to high concentrations of interleukin (IL)-15, whereas low doses of IL-15 triggered only phosphorylation of the transcription factor STAT5. mTOR stimulated the growth and nutrient uptake of NK cells and positively fed back on the receptor for IL-15. [Nat Immunol] Abstract
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PUBLICATIONS (Ranked by impact factor of the journal)
Id2 and Id3 Maintain the Regulatory T Cell Pool to Suppress Inflammatory Disease
Investigators showed that expression of Id2 and Id3 in regulatory T cells was required to suppress development of fatal inflammatory disease. [Nat Immunol] Abstract

Non-Self Recognition by Monocytes Initiates Allograft Rejection
Scientists demonstrate that danger signals associated with dying cells are not sufficient to initiate alloimmunity, but that recognition of allogeneic non-self by the innate immune system is required. [J Clin Invest] Full Article

Recipient NK Cell Inactivation and Intestinal Barrier Loss Are Required for MHC-Matched Graft-versus-Host Disease
Recipient natural killer (NK) cells prevented minor mismatch (major histocompatibility complex [MHC]-matched) graft-versus-host disease (GvHD) by limiting expansion and target organ infiltration of alloreactive T cells via a perforin-dependent mechanism, revealing an immunoregulatory function of MHC-matched recipient NK cells in GvHD. [Sci Transl Med] Abstract

Androgens Alter T-Cell Immunity by Inhibiting T-Helper 1 Differentiation
Investigators evaluated the effect of androgens on murine and human T cells in vivo and in vitro. They found that murine androgen deprivation in vivo elicited RNA expression patterns conducive to IFN signaling and T-cell differentiation. [Proc Natl Acad Sci USA] Abstract

Tolerogenic Dendritic Cells Specific for β2-Glycoprotein-I Domain-I, Attenuate Experimental Antiphospholipid Syndrome
Scientists aimed to uncover the tolerance efficacy attributed to beta-2-glycoprotein-I (β2GPI) tolerogenic dendritic cells (tDCs) or β2GPI domain-I and domain-V-tDCs in mice with antiphospholipid syndrome. [J Autoimmun] Abstract

Trif-Dependent Induction of Th17 Immunity by Lung Dendritic Cells
Researchers identified novel roles of the adaptor protein TRIF (TIR-domain-containing adapter-inducing interferon-β) in neutrophilic responses to inhaled allergens. In different mouse models of asthma, Trif-deficient animals had marked reductions in interleukin-17, airway neutrophils, and airway hyperresponsiveness compared with wild-type mice, whereas airway eosinophils were generally similar in these two strains. [Mucosal Immunol] Abstract

Regulatory T Cells Influence Blood Flow Recovery in Experimental Hindlimb Ischemia in an IL-10 Dependent Manner
Researchers hypothesized that adoptive regulatory T cell transfer and depletion influences reestablishment of flow in a hindlimb ischemia model and that this effect is mediated by the cytokine IL-10. [Cardiovasc Res] Abstract

Mammalian Target of Rapamycin Complex 2 Modulates αβTCR Processing and Surface Expression during Thymocyte Development
Scientists found that deletion of the mammalian target of rapamycin complex 2 component rictor at early stages of T cell development led to aberrant maturation and increased proteasomal degradation of nascent TCRs. Although CD127 expression became elevated, the levels of TCRs as well as CD4, CD8, CD69, Notch, and CD147 were significantly attenuated on the surface of rictor-deficient thymocytes. [J Immunol] Abstract

Hepatocytes Induce Foxp3+ Regulatory T Cells by Notch Signaling
Investigators showed that murine hepatocytes (HCs) induced Foxp3+ regulatory T cells (Tregs) within CD4+ T cells in vitro, which increased in the presence of TGF-β. A further Foxp3+ Treg expansion was observed if HCs were isolated from regenerated livers. [J Leukoc Biol] Abstract

Distinct Spatial Distribution of Microglia and Macrophages following Mesenchymal Stem Cell Implantation in Mouse Brain
Although Iba1+ CX3CR1+ myeloid cells are considered to be of resident microglial origin, Iba1+ CX3CR1 myeloid cells are most likely of peripheral monocyte/macrophage origin. In order to confirm the latter, researchers performed mesenchymal stem cell-blue fluorescent protein grafting experiments in the central nervous system of eGFP+ bone marrow chimeric C57BL/6 mice. [Immunol Cell Biol] Full Article

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Whitepaper: Automated Cell Isolation Enables More Relevant HIV Models
TREG-Cell Therapies for Autoimmune Rheumatic Diseases
The authors discuss three potential strategies for the clinical use of regulatory T (TREG) cells to treat autoimmune rheumatic disease: expansion of self-antigen-specific natural TREG cells in vivo; propagation of antigen-specific natural TREG cells ex vivo, by in vitro antigenic stimulation, and subsequent transfer back into the host; or conversion of antigen-specific conventional T cells into TREG cells in vivo or ex vivo. [Nat Rev Rheumatol] Abstract

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Regeneus Enters into US Marketing Trial Agreement for Novel Canine Cancer Vaccine
Regeneus announced that it has entered into an agreement with a leading US vet health care services group to conduct a marketing trial in the United States of the company’s novel autologous canine therapeutic cancer vaccine, Kvax. The therapeutic vaccine stimulates the dog’s immune system to see the cancer cells as foreign and helps prevent further growth of the tumor and the development of new tumors. [Regeneus Ltd.] Press Release

TxCell to Lead POSITIVE Project to Automate First Production Step of Ovasave®, Its Lead Personalized Cellular Immunotherapy
TxCell SA announced the launch of, and funding awarded to, the POSITIVE project in collaboration with the Gene and Cell Therapy Unit developing new antiviral cell-based immunotherapies and Biosafe, a Swiss private company. [TxCell SA] Press Release

Merck’s Investigational Anti-PD-1 Antibody, Pembrolizumab, under Regulatory Review in Europe for the Treatment of Advanced Melanoma
Merck announced the European Medicines Agency has accepted for review a marketing authorization application for pembrolizumab, the company’s investigational anti-PD-1 antibody, for the treatment of advanced melanoma. [Merck & Co., Inc.] Press Release

Amgen Receives FDA Breakthrough Therapy Designation for Investigational BiTE® Antibody Blinatumomab in Acute Lymphoblastic Leukemia
Amgen announced that the U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy Designation to investigational bispecific T cell engager (BiTE®) antibody blinatumomab, for adults with Philadelphia-negative relapsed/refractory B-precursor acute lymphoblastic leukemia, a rapidly progressing cancer of the blood and bone marrow. [Amgen Inc.] Press Release

ImmunID Announces Agreement with the Singapore Immunology Network (SIgN) to Study Immune Competence
ImmunID embarked on an agreement with SIgN. Under the agreement, ImmunID will use its proprietary ImmunTraCkeR® and ImmunIG® tests to evaluate T and B immune repertoire diversity in the blood of patients enrolled in a SIgN-led clinical trial. [ImmunID Technologies] Press Release

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NEW 13th International Symposium on Dendritic Cells
September 14-18, 2014
Tours, France

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NEW Research Officer – Human Immunology (National Research Council Canada)

NEW Postdoctoral Fellow – Immune Mechanisms in Diabetes (Joslin Diabetes Center/Harvard Medical School)

Principal Investigator Positions – Systems & Synthetic Biology (Institute for Research in Immunology and Cancer)

Postdoctoral Positions – Inflammation in the Development of Chronic and Highly Prevalent Diseases (University of Pennsylvania and Children’s Hospital of Philadelphia)

Postdoctoral Scientist – Immune Focused In Vitro Analytics (Celentyx Ltd.)

Postdoctoral Position – Signaling and Gene Expression in Immune Cells (Universitat Pompeu Fabra)

Postdoctoral Position – Cell Death and Inflammation (Inflammation Research Center – VIB-UGent)

Postdoctoral Fellow – Microbiology and Immunology (McGill University)

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

Scientist – Recombinant Molecules and Antibodies (STEMCELL Technologies Inc.)

Scientist – Pluripotent Stem Cell Media Development, High Throughput Screening (STEMCELL Technologies Inc.)

Scientist – Cell Culture Support Products (STEMCELL Technologies Inc.)

Scientist – Immunology/Cell Separation (STEMCELL Technologies Inc.)

Research Associate – Cell Separation (STEMCELL Technologies Inc.)

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