Volume 6.16 | May 9

Immune Regulation News 6.16 May 9, 2014
Immune Regulation News
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Discovery Helps Explain How B Cells Adapt to Their Targets
Researchers looked at what happens to B cells during their time in the two zones of the germinal center. In the “dark” zone, B cells mutate and proliferate before traveling to the “light” zone, where those with antibodies that bind best to the microbial antigens are selected. The B cells then continue to divide, returning to the dark zone. [Press release from The Rockefeller University discussing online prepublication in Nature]
Press Release | Abstract
A New System for High-Throughput Cell Isolation Directly from Whole Blood
PUBLICATIONS (Ranked by impact factor of the journal)
Cancer Immunotherapy Based on Mutation-Specific CD4+ T Cells in a Patient with Epithelial Cancer
Researchers used a whole-exomic-sequencing-based approach to demonstrate that tumor-infiltrating lymphocytes (TIL) from a patient with metastatic cholangiocarcinoma contained CD4+ T helper 1 (TH1) cells recognizing a mutation in erbb2 interacting protein expressed by the cancer. After adoptive transfer of TIL containing about 25% mutation-specific polyfunctional TH1 cells, the patient achieved a decrease in target lesions with prolonged stabilization of disease. [Science] Abstract | Press Release

Rad50-CARD9 Interactions Link Cytosolic DNA Sensing to Interleukin-1β Production
Scientists defined a cytosolic DNA-recognition pathway for inflammation and a physical and functional connection between a conserved DNA-damage sensor and the innate immune response to pathogens. [Nat Immunol] Abstract | Press Release

Tumor Endothelium FasL Establishes a Selective Immune Barrier Promoting Tolerance in Tumors
Researchers found the death mediator Fas ligand (FasL) expression was associated with scarce CD8+ infiltration and a predominance of FoxP3+ T regulatory (Treg) cells. Tumor-derived vascular endothelial growth factor A, interleukin 10 and prostaglandin E2 cooperatively induced FasL expression in endothelial cells, which acquired the ability to kill effector CD8+ T cells but not Treg cells because of higher levels of c-FLIP expression in Treg cells. [Nat Med] Abstract

IL-22+CD4+ T Cells Promote Colorectal Cancer Stemness via STAT3 Transcription Factor Activation and Induction of the Methyltransferase DOT1L
Investigators detected interleukin-22 (IL-22) in patient colorectal cancer tissues that was produced predominantly by CD4+ T cells. In a mouse model, migration of these cells into the colon cancer microenvironment required the chemokine receptor CCR6 and its ligand CCL20. [Immunity] Abstract | Graphical Abstract | Press Release

Downmodulation of Tumor Suppressor p53 by T Cell Receptor Signaling Is Critical for Antigen-Specific CD4+ T Cell Responses
Downmodulation of tumor suppressor p53 in response to antigen stimulation was found critical for antigen-specific T cell proliferation, and preventing p53 degradation by inhibiting regulating protein Mdm2 prevented antigen-specific T cell proliferation. [Immunity] Abstract | Graphical Abstract

IL-27 and IL-12 Oppose Pro-Inflammatory IL-23 in CD4+ T Cells by Inducing Blimp1
Researchers identified the transcriptional regulator Blimp1 as crucial to induce IL-10 in inflammatory T helper cells. Pre-committed T helper 17 cells responded to IL-27 and IL-12 by upregulating Blimp1 and adopt a Tr1-like phenotype characterized by IL-10 and interferon-γ production. [Nat Commun] Abstract

IL-21 Induces IL-22 Production in CD4+ T Cells
Scientists showed that interleukin (IL)-21 triggers IL-22, but not IL-17 production by CD4+ T cells. Signal transducer and activator of transcription 3, activated by IL-21, controls the epigenetic status of the il22 promoter and its interaction with the aryl hydrocarbon receptor (AhR). IL-21 and AhR signaling in T cells control IL-22 production and the development of dextran sodium sulfate-induced colitis in innate lymphoid cell-deficient mice. [Nat Commun] Abstract

Ubiquitination by SAG Regulates Macrophage Survival/Death and Immune Response during Infection
Using in vitro and ex vivo approaches, investigators showed that macrophage survival is synchronized by SAG (sensitive to apoptosis gene), which is a key member of the ubiquitin-proteasome system. [Cell Death Differ] Full Article

The Oxysterol Receptor LXRβ Protects against DSS- and TNBS-Induced Colitis in Mice
Scientists found inflammatory cytokines and chemokines were increased together with increased infiltration of immune cells in the colon epithelium in Lxr-deficient mice. Activation of oxysterol receptors (LXRs) strongly suppressed expression of inflammatory mediators including TNFα. While LXRα had anti-inflammatory effects in CD11b+ immune cell populations, LXRβ in addition had anti-inflammatory effects in colon epithelial cells. [Mucosal Immunol] Abstract

Single-Cell RNA Sequencing Reveals T Helper Cells Synthesizing Steroids De Novo to Contribute to Immune Homeostasis
Investigators demonstrate production of the steroid pregnenolone by T helper 2 (Th2) cells in vitro and in vivo in a helminth infection model. Single-cell RNA sequencing and quantitative PCR analysis suggest that pregnenolone synthesis in Th2 cells is related to immunosuppression. [Cell Rep]
Full Article | Graphical Abstract | Press Release

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Free Nature Reviews Immunology Poster: The Immune Response to HIV
A Naturally Occurring CD8+CD122+ T-Cell Subset as a Memory-Like Treg Family
The authors summarize significant progress in the promising field of CD8+CD122+ regulatory T cell (Treg) research and discuss their phenotypes, suppressive roles in autoimmunity and alloimmunity, functional requirements, mechanisms of action and potential applications in the clinic. [Cell Mol Immunol] Abstract

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Kadmon Corporation Presents Results of KD025 Preclinical and Clinical Studies
Kadmon Corporation, LLC announced the presentation of preclinical and clinical data from studies of KD025, the Company’s Phase II, orally bioavailable, potent and highly selective inhibitor of Rho-associated coiled-coiled kinase 2, used in models of autoimmune disease such as a collagen induced arthritis and lupus. [Press release from Kadmon Corporation, LLC discussing research presented at the American Association of Immunologists (AAI) Annual Meeting, Pittsburgh] Press Release | Poster

MacroGenics Presents Pre-Clinical Data on Inhibition of Autoimmune Diseases with DART Candidate MGD010
MacroGenics Inc. presented pre-clinical data on MGD010, a bi-specific Dual-Affinity Re-Targeting (DART®) protein, demonstrating its ability to inhibit B-cell activation without B-cell depletion, which could provide a novel treatment option for patients with autoimmune disorders. [Press release from MacroGenics Inc. discussing research presented at the American Association of Immunologists (AAI) Annual Meeting, Pittsburgh]
Press Release

OncoSec Medical Presents New Data
OncoSec Medical Inc. presented preliminary experimental findings demonstrating that electroporation with DNA-based IL-12 in mice can lead to systemic anti-tumor immune responses in distant untreated lesions. These data are consistent with the previously reported findings in melanoma patients treated in the Phase II OMSI100 study [Press release from OncoSec Medical Inc. discussing research presented at the 10th Annual PEGS: The Essential Protein Engineering Summit, Boston] Press Release

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Debiopharm Group™ and Yale University Extend and Broaden Their Collaboration for the Discovery and Development of MIF Inhibitors to Treat Autoimmune and Inflammatory Diseases
Debiopharm Group™ signed a new license and research agreement with Yale University regarding the discovery of Macrophage Migration Inhibitory Factor (MIF) inhibitors for treatment of autoimmune and inflammatory diseases. [Debiopharm Group™] Press Release

CMC Biologics and MacroGenics Enter into a Process Development and Manufacturing Agreement for Oncology Product Candidate
CMC Biologics, Inc. and MacroGenics, Inc., a clinical-stage biopharmaceutical company focused on discovering and developing innovative monoclonal antibody-based therapeutics for the treatment of cancer and autoimmune diseases, have entered into an agreement to further develop the production process for transfer and clinical manufacturing of one of MacroGenics’ product candidates. [CMC Biologics, Inc.] Press Release

Outwitting Immunity to Treat Disease: Start-Up Raises 33 Million CHF
EPFL start-up Anokion has the immune system in its sights. The company has developed technology for retraining white blood cells that holds promise for treating autoimmune, allergic, and a number of other diseases. A group of private investors have pledged 33 million Swiss francs (37 million dollars) into the young company. [École Polytechnique Fédérale de Lausanne] Press Release

Medical College of Wisconsin Receives Grant from National Cancer Institute to Develop Novel Cellular Immunotherapy
The Medical College of Wisconsin has received a five-year, $1.6 million grant from the National Institutes of Health’s National Cancer Institute to support development of novel immune cell-based therapies to cancer. [Medical College of Wisconsin] Press Release
National Institutes of Health (United States)

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Center for Biologics Evaluation and Research (United States)

European Medicines Agency (European Union)

Medicines and Healthcare Products Regulatory Agency (United Kingdom)

Therapeutic Goods Administration (Australia)
NEW FASEB Science Research Conferences – Translational Neuroimmunology: From Mechanisms to Therapeutics
July 13-18, 2014
Big Sky, United States

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NEW Principal Investigator – Molecular Mechanisms of Inflammation (Inflammation Research Center – VIB-UGent)

NEW Postdoctoral Fellow – Microbiology and Immunology (McGill University)

Postdoctoral Research Associate – Functional Cross-Talk between T Lymphocytes and NK Cells (Meharry Medical College School of Medicine)

Postdoctoral Associate/Research Scientist – Macrophage Biology (Massachusetts Institute of Technology – MIT)

Postdoctoral Position – Intestinal Immunology (Biomedical Sciences Research Center “Alexander Fleming”)

Postdoctoral Associate – Immunology (Virginia Bioinformatics Institute at Virginia Tech)

Postdoctoral Position – Immunology (University of Pittsburgh)

Director of GMP/GLP Quality Operations (University of Pennsylvania, Perelman School of Medicine)

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

Research Associate – Cell Separation (STEMCELL Technologies Inc.)

Research Technologist – hPSC (STEMCELL Technologies Inc.)

Research Technologist – Pluripotent Stem Cells (STEMCELL Technologies Inc.)

Research Technologist – PSC Biology and Bioengineering (STEMCELL Technologies Inc.)

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