Volume 5.17 | May 10

Immune Regulation News 5.17 May 10, 2013
     In this issue: Publications | Reviews | Industry News | Policy News | Events | Jobs
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TOP STORY
IRF4 Transcription-Factor-Dependent CD103+CD11b+ Dendritic Cells Drive Mucosal T Helper 17 Cell Differentiation
Scientists demonstrated that intestinal CD103+CD11b+ dendritic cell (DC) survival was dependent on interferon regulatory factor 4 (IRF4). Mice with a DC deletion in Irf4 displayed reduced numbers of intestinal interleukin 17-secreting helper T 17 (Th17) cells and failed to support Th17 cell differentiation in draining mesenteric lymph nodes following immunization. [Immunity] Abstract | Graphical Abstract

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PUBLICATIONS (Ranked by impact factor of the journal)

Immune Surveillance by CD8αα+ Skin-Resident T Cells in Human Herpes Virus Infection
Using cell-type-specific laser capture microdissection, transcriptional profiling and T-cell antigen receptor β-chain genotyping on sequential genital skin biopsies, investigators showed that CD8αα+ T cells are the dominant resident population of dermal-epidermal junction (DEJ) CD8+ T cells that persist at the site of previous herpes simplex virus 2 reactivation. CD8αα+ T cells located at the DEJ lack chemokine-receptor expression required for lymphocyte egress and recirculation, express gene signatures of T-cell activation and antiviral activity, and produce cytolytic granules during clinical and virological quiescent time periods. [NatureAbstract | Press Release

IL-2-Dependent Tuning of NK Cell Sensitivity for Target Cells Is Controlled by Regulatory T Cells
The authors hypothesized whether regulatory T (T reg) cells are required to restrain NK cells, the third lymphocyte lineage, whose features combine innate and adaptive immune cell properties. Although depletion of Treg cells led to systemic fatal autoimmunity, NK cell tolerance and reactivity to strong activating self- and non-self-ligands remained largely intact. [J Exp Med] Abstract

Plasmacytoid Dendritic Cells Promote Rotavirus-Induced Human and Murine B Cell Responses
Human in vitro and murine in vivo models of rotavirus infection were used to delineate the role of primary plasmacytoid DCs in initiating B cell responses.  [J Clin Invest] Full Article

Forced miR-146a Expression Causes Autoimmune Lymphoproliferative Syndrome in Mice via Downregulation of Fas in Germinal Center B Cells
To elucidate the function of microRNA (miR)-146a in vivo, researchers generated a transgenic mouse line overexpressing miR-146a. Starting at an early age, these transgenic mice developed spontaneous immune disorders mimicking human autoimmune lymphoproliferative syndrome with distinct manifestations, including enlarged spleens and lymph nodes, inflammatory infiltration in the livers and lungs, increased levels of double-negative T cells in peripheral blood, and increased serum IgG levels. [Blood] Abstract

Peptide Library-Based Evaluation of T-Cell Receptor Breadth Detects Defects in Global and Regulatory Activation in Human Immunologic Diseases
Using combinatorial peptide libraries, investigators functionally measured broad T-cell reactivity and observed impaired reactivity in established models of T-cell receptor repertoire restriction and in previously unrecognized disease contexts. By concurrently analyzing T-regulatory and T-effector cells, they showed strong functional correlation between these subsets in healthy individuals and, strikingly, that alterations of this balance are associated with T helper type 2-mediated disease in a lymphopenic setting. [Proc Natl Acad Sci USA] Abstract

Regulatory T Cell-Derived IL-10 Ameliorates Crescentic GN
Using IL-10 reporter mice, scientists detected IL-10-producing Foxp3+ T cells in the kidney, blood, and secondary lymphoid tissue in a mouse model of crescentic GN. Specific inactivation of Il10 in Foxp3+ regulatory T cells (Tregs) eliminated the ability of these cells to suppress renal and systemic production of IFNγ and IL-17; these IL-10-deficient Tregs lost their capacity to attenuate renal tissue injury. [J Am Soc Nephrol] Abstract

TIE-2 and VEGFR Kinase Activities Drive TIE-2-Expressing Monocytes Immunosuppressive Function in Human Breast Tumors
The authors investigated the changes in TIE-2-expressing monocytes (TEM) immunosuppressive activity and gene expression in response to specific kinase inhibitors of TIE-2 and VEGFR. The ability of tumor TEM to suppress tumor-specific T cell response mediated by tumor dendritic cells was measured in vitro. [Clin Cancer Res] Abstract

Engineered Regulatory T Cells Coexpressing MHC Class II: Peptide Complexes Are Efficient Inhibitors of Autoimmune T Cell Function and Prevent the Development of Autoimmune Arthritis
Using a retroviral expression system encoding Foxp3 and HLA-DR1 covalently linked to the immunodominant peptide of the autoantigen type II collagen (DR1-CII), naive T cells were engineered to become regulatory T cells that express DR1-CII complexes on their surface. [J Immunol] Abstract

Roles of Adipocytes and Fibroblasts in Activation of the Alternative Pathway of Complement in Inflammatory Arthritis in Mice
Results demonstrated that pathogenic activation of the alternative pathway (AP) can occur in the joint through immune complexes adherent to cartilage and the local production of necessary AP proteins by adipocytes and fibroblast-like synoviocytes. [J Immunol] Abstract | Press Release

The Immunologically Active Oligosaccharides Isolated from Wheatgrass Modulate Monocytes via Toll-Like Receptor-2 Signaling
Wheatgrass-derived oligosaccharides (WG-PS3) were isolated and found to induce CD69 and Th1 cytokine expression in human peripheral blood mononuclear cells. In particular, WG-PS3 directly activated the purified monocytes by inducing the expression of CD69, CD80, CD86, IL-12, and TNF-α but affected NK and T cells only in the presence of monocytes. [J Biol Chem] Abstract | Full Article

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REVIEWS

Cell-Based Immunotherapy against Gliomas: From Bench to Bedside
Cellular immunotherapy is currently being explored as therapeutic approach to treat malignant brain tumors. This review discusses advances in active, passive, and vaccine-based immunotherapeutic strategies for gliomas both at the bench and in the clinic. [Mol Ther] Abstract

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

INDUSTRY NEWS

USC Norris Comprehensive Cancer Center Studies Target Immune System, Women’s Cancers
The University of Southern California (USC) Norris Comprehensive Cancer Center, a part of the Keck School of Medicine, has recently begun recruiting female participants for three new clinical trials studying breast, ovarian and cervical cancer immunotherapies. It is scheduled to open recruitment for a second ovarian cancer study over the summer. [University of Southern California] Press Release

Cell Medica Announces Treatment of First Pediatric Patient in Early Stage Clinical Trial of Cytovir ADV
Cell Medica announced the treatment of the first patient in the ASPIRE Trial, an early stage Phase I/II clinical study investigating the safety and efficacy of CytovirTM ADV for the treatment of adenovirus infections in immunosuppressed pediatric patients following bone marrow transplantation. Cytovir ADV is comprised of naturally occurring T lymphocyte cells which demonstrate immune response functions when exposed to adenovirus antigens. [Cell Medica] Press Release

Oxford BioMedica Announces Lentiviral Vector Development and Manufacturing Collaboration
Oxford BioMedica plc announced that it has signed an agreement with Novartis to manufacture clinical grade material utilizing Oxford BioMedica’s LentiVector® gene delivery technology. Oxford BioMedica will be responsible for manufacturing several batches of a lentiviral vector encoding CTL019 technology.  This vector will be used to transduce patients’ immune cells in an ex vivo process before they are re-infused into patients. [Oxford BioMedica plc] Press Release

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POLICY NEWS

National Institutes of Health (United States)

Food and Drug Administration (United States)

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)

EVENTS

NEW Cell Symposia – Immunometabolism: From Mechanisms to Therapy
June 9-11, 2013
Toronto, Canada


NEW SELECTBIO CellTech 2014
January 28-29, 2014
San Diego, United States

Visit our events page to see a complete list of events in the immune regulation community.

JOB OPPORTUNITIES

NEW PhD Studentship – Role of Epigenetic Regulators in Control of Immunity and Inflammation (King’s College London)

NEW Postdoctoral Researcher – Innate Immunity (Massachusetts General Hospital / Harvard Medical School)

PhD Studentship – The Role of Adipocyte Progenitor Cells during Immune Responses (University of Birmingham)

Postdoctoral Fellowship – Tumor Immunology (Northwestern University – Robert H Lurie Comprehensive Cancer Center)

Postdoctoral Fellow – Immunological Pathways in Human Inflammatory Bowel Disease (Yale University – School of Medicine)

PhD Studentship – Mucosal Immunology (KU Leuven Translational Research Center for Gastrointestinal Disorders)


Postdoctoral Position – Immunology (INSERM 1020)


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