Volume 5.40 | Oct 18

Immune Regulation News 5.40 October 18, 2013
Pulmonary Cell News
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Researchers Identify Mechanism to Control Immune Signaling; Study Points to Treatment of Inflammatory Diseases
Investigators identified a cellular pathway used to deactivate innate immune system signaling – a key discovery that could potentially lead to the development of novel vaccines or clinical treatments for chronic inflammatory diseases such as systemic lupus erythematosus and rheumatoid arthritis. [Press release from University of Miami discussing online prepublication in Cell] Press Release | Abstract | Graphical Abstract
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PUBLICATIONS (Ranked by impact factor of the journal)
Transient Regulatory T Cell Ablation Deters Oncogene-Driven Breast Cancer and Enhances Radiotherapy
The authors investigated the role of regulatory (T reg) cells in murine mammary carcinogenesis using an orthotopic, polyoma middle-T antigen-driven model in Foxp3DTR knockin mice. T reg cell ablation resulted in significant determent of primary and metastatic tumor progression. Importantly, short-term ablation of T reg cells in advanced spontaneous tumors led to extensive apoptotic tumor cell death. [J Exp Med] Abstract

Smurf2 Suppresses B-Cell Proliferation and Lymphomagenesis by Mediating Ubiquitination and Degradation of YY1
Researchers showed that Smurf2 mediates ubiquitination and degradation of YY1, a key germinal center transcription factor. Smurf2 deficiency enhances YY1-mediated transactivation of c-Myc and B-cell proliferation. [Nat Commun] Abstract

Exocytosis Acts as a Modulator of the ILT4-Mediated Inhibition of Neutrophil Functions
Scientists showed that primary human neutrophils expressed immunoglobulin-like transcript 4 (ILT4) inhibitory receptor and that this expression was induced during differentiation of the myelomonoblast PLB-985 cell line into “neutrophil-like” cells. Functional assays indicated that human leukocyte antigen G, the preferred ligand of ILT4, inhibited the phagocytic function of neutrophils. [Proc Natl Acad Sci USA] Abstract

CX3CR1+ Cells Facilitate the Activation of CD4 T Cells in the Colonic Lamina Propria during Antigen-Driven Colitis
To investigate whether CX3CR1+ phagocytes communicate with CD4 T cells during the development of transfer colitis, the authors established an antigen-driven colitis model induced by the adoptive transfer of DsRed OT-II cells in CX3CR1GFP/+ × RAG−/− recipients challenged with Escherichia coli expressing ovalbumin fused to a cyan fluorescent protein. [Mucosal Immunol] Abstract

Distinct Temporal Patterns of T Cell Receptor Signaling during Positive versus Negative Selection In Situ
In vitro studies indicate that peptide ligands that induce positive selection stimulate a low, but sustained, pattern of T cell receptor (TCR) signaling; however, the temporal pattern of TCR signaling in MHC class I-restricted thymocytes in the thymus, under conditions that support positive selection, is unknown. Researchers addressed this question by examining intracellular Ca2+ dynamics and migratory changes in thymocytes undergoing positive and negative selection in thymic slices. [Sci Sig] Abstract

Particle Shape Dependence of CD8+ T Cell Activation by Artificial Antigen Presenting Cells
The ellipsoidal biomimetic antigen presenting cells (aAPCs) with high-aspect ratios showed significantly enhanced in vitro and in vivo activity above spherical aAPCs with particle volume and antigen content held constant. Confocal imaging indicates that CD8+ T cells preferentially migrate to and are activated by interaction with the long axis of the aAPC. [Biomaterials] Abstract | Press Release

IL-32-PAR2 Axis Is an Innate Immunity Sensor Providing Alternative Signaling for Lipopolysaccharide-TRIF Axis
The authors found that interleukin (IL)-32γ upregulated serine protease activity of proteinase-3 (PR3), in turn triggering protease-activated receptor 2 (PAR2) signaling. Interestingly, silencing of PR3 or PAR2 using siRNA markedly diminished IL-32γ-induced TNFα and IFN-β mRNA expression. [Sci Rep] Full Article

IL-21 Modulates Activation of NKT Cells in Patients with Stage IV Malignant Melanoma
In a phase IIa trial of patients with metastatic melanoma, investigators analyzed the frequency and function of natural killer T (NKT) cells in patients receiving recombinant IL-21 (rIL-21). NKT cells were present at a low frequency, but their levels were relatively stable in patients administered rIL-21. [Clin & Transl Immunol] Full Article

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Mechanical Regulation of T-Cell Functions
The authors review existing data on how force regulates protein conformational changes and interactions with counter molecules, including integrins, actin, and the T-cell receptor, and how each relates to T-cell functions. [Immunol Rev] Abstract

Cofilin: A Redox Sensitive Mediator of Actin Dynamics during T-Cell Activation and Migration
Cofilin is an actin-binding protein that depolymerizes and/or severs actin filaments. This dual function of cofilin makes it one of the major regulators of actin dynamics important for T-cell activation and migration. The activity of cofilin is spatio-temporally regulated. [Immunol Rev] Full Article

Gut TFH and IgA: Key Players for Regulation of Bacterial Communities and Immune Homeostasis
This review discusses the finely tuned regulatory mechanisms for Immunoglobulin A (IgA) synthesis in germinal centers of Peyer’s patches and emphasize the roles of CD4+ T cells for IgA selection and the maintenance of appropriate gut microbial communities required for immune homeostasis. [Immunol Cell Biol] Abstract

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

The IBC’s 24th Annual Antibody Engineering & Therapeutics meeting is your opportunity to attend the industry's most important scientific and networking meeting in the antibody field.
New Grant to Broaden Exploitation of Promising Immunotherapy to Many Blood Cancers
Researchers from the Center for Cell and Gene Therapy at Baylor College of Medicine, Texas Children’s Hospital and Houston Methodist Hospital have received a $6.25 million, five-year grant from the Leukemia & Lymphoma Society to extend their promising work with T-cell immunotherapies beyond lymphoma to other types of blood cancers including myeloma and acute lymphoblastic leukemia. [Baylor College of Medicine] Press Release

Kadmon Corporation Announces Development Plans for Selective ROCK 2 Inhibitor, KD025, in Psoriasis, Lupus Nephritis and NASH
Kadmon Corporation, LLC, announced plans for the initiation of three clinical studies of KD025, an orally bioavailable, potent and highly selective inhibitor of ROCK 2 (Rho-associated coiled-coiled kinase 2), in each of three indications: psoriasis, lupus nephritis and non-alcoholic steatohepatitis (NASH). [Kadmon Corporation, LLC] Press Release

The Terry Fox Foundation Tackles “Unmet Cancer Needs” with $13.6 Million for Rare Tumor, Lymphoma and Early-Stage Prostate and Esophageal Cancer Research
Three exemplary Canadian cancer research teams are receiving $13.6 million from the Terry Fox Foundation to conduct cutting-edge research in several areas where there are unmet cancer needs. [The Terry Fox Foundation] Press Release

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NEW IMMUNOLOGY 2014™American Association of Immunologists (AAI) Annual Meeting
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Visit our events page to see a complete list of events in the immune regulation community.
NEW Postdoctoral Position – Lymphocyte Motility (INSERM)

Postdoctoral Fellow – Anti-Tumor Immunity (H. Lee Moffitt Cancer Center & Research Institute)

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)

Research Fellow – Immunology (Queen’s University Belfast)

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

Postdoctoral Fellowship – Immunology (Johns Hopkins University School of Medicine)

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 Technologist – Cell Culture Media & Matrices (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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