Immune Regulation News Volume 5.26 | Jul 12 2013

T Cell-Derived Protein S Engages TAM Receptor Signaling in Dendritic Cells to Control the Magnitude of the Immune Response
Researchers identified a mechanism of immune homeostasis by which adaptive immunity, once triggered, tempers dendritic cell (DC) activation and prevents overreactive immune responses. T cells, once activated, produced Protein S that signaled through TAM receptor tyrosine kinases in DCs to limit the magnitude of DC activation. [Immunity] Abstract

TCR-Ligand k_off Rate Correlates with the Protective Capacity of Antigen-Specific CD8⁺ T Cells for Adoptive Transfer
T cell receptor (TCR) transfer experiments indicate that a major part of avidity is hardwired within the structure of the TCR. Unfortunately, rapid measurement of structural avidity of TCRs is difficult on living T cells. Scientists developed a technology where dissociation (k_off) of truly monomeric peptide-major histocompatibility complex molecules bound to surface-expressed TCRs can be monitored by real-time microscopy in a highly reliable manner. [Sci Transl Med] Abstract | Press Release

Plasmacytoid Dendritic Cells, Interferon Signaling, and Fcγ Receptor Contribute to Pathogenesis and Therapeutic Response in Childhood Immune Thrombocytopenia
The authors showed that monocytes from patients with immune thrombocytopenia (ITP) have a distinct gene expression profile, with increased expression of type I interferon response genes. Plasma from ITP patients had increased levels of several cytokines indicative of immune activation, including an increase in interferon-α. ITP patients also had an increase in plasmacytoid dendritic cells compared to healthy donors. [Sci Transl Med] Abstract

Modulation of Natural Killer Cell Antitumor Activity by the Aryl Hydrocarbon Receptor
Investigators showed that aryl hydrocarbon receptor (AhR) expression is induced in murine natural killer (NK) cells upon cytokine stimulation. They showed that in the absence of AhR, NK cells have reduced cytolytic activity and reduced capacity to control RMA-S tumor formation in vivo, despite having normal development and maturation markers. [Proc Natl Acad Sci USA] Abstract

Pleurocidin, a Novel Antimicrobial Peptide, Induces Human Mast Cell Activation through the FPRL1 Receptor
As cathelicidins stimulate mast cell chemotaxis and mediator release, scientists postulated that pleurocidins similarly activate mast cells. A screen of 20 pleurocidin peptides revealed that some were capable of degranulating the human mast cell line Laboratory of Allergic Diseases 2. [Mucosal Immunol] Abstract

Characterization of Human Antiviral Adaptive Immune Responses during Hepatotropic Virus Infection in HLA-Transgenic Human Immune System Mice
The authors analyzed human antiviral immunity in humanized mice during a hepatotropic adenovirus infection. They compared immune responses of conventional humanized NOD SCID IL-2Rγ-deficient mice to those of a novel NOD SCID IL-2Rγ-deficient strain transgenic for both HLA-A*0201 and a chimeric HLA-DR*0101 molecule. [J Immunol] Abstract

Protein Interaction Networks in Innate Immunity
Recent technological advances have empowered approaches to investigate innate immune signaling and monitor host-pathogen interactions at a systems level. Protein complexes are key players in pathogen recognition and integrate much of the host molecular responses that occur at the transcriptional and translational level. The ability to monitor protein complex abundance, dynamics, and composition is therefore important to understand the ability of cells to mount the appropriate immune response. [Trends Immunol] Abstract

Regulatory T Cells and Transplantation Tolerance
Recent advances in understanding the molecular and epigenetic mechanisms underlying the induction and stabilization of Foxp3 expression, thus guiding Foxp3⁺ regulatory T cell (Treg) differentiation, have revealed novel therapeutic targets in animal models that can be translated to harness Foxp3⁺ Tregs from within the patient. Such in vivo induced Foxp3⁺ Tregs can also induce the tolerant state. Pharmacological compounds are available to exploit these targets and their further development holds great promise for clinical translation. [Immunotherapy] Abstract

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MCW Researcher to Study Main Complication after Bone Marrow Transplantation
The Medical College of Wisconsin (MCW) has received a four year, $1.5 million grant from the National Institute of Health’s National Heart, Lung and Blood Institute to study graft versus host disease (GvHD), the major complication associated with bone marrow transplants. In this study, Dr. Drobyski will define the role of specific regulatory T cell populations in GvHD, in order to develop strategies that will help patients better tolerate transplantation. [Medical College of Wisconsin] Press Release

Cellectis Group Announces Groundbreaking In Vivo Proof of Concept Testing of Their Flagship UCART19 Product for Curative Therapy of Leukemia
Cellectis announced the successful in vivo proof of concept testing of their flagship UCART19 product for curative therapy of leukemia. UCART19 is a revolutionary engineered T-cell product that leverages Cellectis’ core technologies in genome engineering. [Cellectis] Press Release

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NEW PhD Research Position – Immune Tolerance and Autoimmunity (Weizmann Institute of Science)

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PhD Position – Cellular Signaling in the Immune System (Helmholtz Centre for Environmental Research – UFZ – Helmholtz Association)

PhD Position – MMP-9 Domain Structure Involvement in Immunomodulation (KU Leuven)

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

Postdoctoral Position – Complement System in Acute and Chronic Inflammatory Diseases (Institute for Systemic Inflammation Research, University of Lübeck)

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Postdoctoral Position – Mechanistic Studies in Immune Responses (Medical University of Vienna)

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