Immune Regulation News Volume 5.31 | Aug 16 2013

Local Proliferation Dominates Lesional Macrophage Accumulation in Atherosclerosis
In murine atherosclerotic lesions, investigators found that macrophages turn over rapidly, after four weeks. Replenishment of macrophages in these experimental atheromata depends predominantly on local macrophage proliferation rather than monocyte influx. [Nat Med] Abstract | Press Release

Enveloped Viruses Disable Innate Immune Responses in Dendritic Cells by Direct Activation of TAM Receptors
Investigators find that ligand-coated viruses activate Tyro3/Axl/Mer (TAM) receptors on dendritic cells, dampen type I interferon signaling, and thereby evade host immunity and promote infection. [Cell Host Microbe] Abstract | Press Release

LRRFIP2 Negatively Regulates NLRP3 Inflammasome Activation in Macrophages by Promoting Flightless-I-Mediated Caspase-1 Inhibition
The precise molecular mechanism for negative regulation of NLRP3 inflammasome activation needs to be further defined. Here, the authors identified leucine-rich repeat Fli-I-interacting protein 2 (LRRFIP2) as an NLRP3-associated protein and an inhibitor for NLRP3 inflammasome activation. [Nat Commun] Full Article

Defective Immune Responses in Mice Lacking LUBAC-Mediated Linear Ubiquitination in B Cells
The authors describe a mouse model (B-HOIP^Δlinear) in which the linear polyubiquitination activity of linear ubiquitin chain assembly complex (LUBAC) is specifically ablated in B cells. Canonical NF-κB and ERK activation, mediated by the tumor necrosis factor receptor superfamily receptors CD40 and TACI, was impaired in B cells from B-HOIP^Δlinear mice due to defective activation of the IKK complex; however, B-cell receptor-mediated activation of the NF-κB and ERK pathways was unaffected. [EMBO J] Abstract

Hyperactivated MyD88 Signaling in Dendritic Cells, through Specific Deletion of Lyn Kinase, Causes Severe Autoimmunity and Inflammation
Investigators demonstrated that hyperactivation of MyD88-dependent signaling in dendritic cells is sufficient to drive pathogenesis of lupus-like disease, illuminating the fact that dysregulation in innate immune cells alone can lead to autoimmunity. [Proc Natl Acad Sci USA] Abstract

Th1 Not Th17 Cells Drive Spontaneous Multiple Sclerosis-Like Disease Despite a Functional Regulatory T Cell Response
Scientists investigated spontaneous central nervous system disease in a clinically relevant, humanized, T cell receptor transgenic mouse model. Mice develop spontaneous, ascending paralysis, allowing unbiased characterization of T cell immunity in an HLA-DR15-restricted T cell repertoire. [Acta Neuropathol] Abstract

Fas Signal Promotes the Immunosuppressive Function of Regulatory Dendritic Cells via ERK/β-Catenin Pathway
The authors showed that CD11b^hiIa^low regulatory dendritic cells (DCs) expressed high level of Fas, and endothelial stromal cell-derived TGF-β could induce high expression of Fas on regulatory DCs via ERK activation. [J Biol Chem] Abstract | Full Article

CDK8-Mediated STAT1-S727 Phosphorylation Restrains NK Cell Cytotoxicity and Tumor Surveillance
Researchers showed that mutation of a single phosphorylation site (Stat1-S727A) enhances natural killer (NK) cell cytotoxicity against a range of tumor cells, accompanied by increased expression of perforin and granzyme B. [Cell Rep] Abstract | Graphical Abstract | Full Article

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BioLife Solutions Expands Strategic Relationship with STEMCELL Technologies
BioLife Solutions, Inc. announced an expansion of its relationship with STEMCELL Technologies Inc. Since August 2009, STEMCELL Technologies has distributed BioLife’s best in class biopreservation media products to the worldwide research and clinical biobanking communities. [BioLife Solutions, Inc.]
Press Release

Seattle Genetics Announces Initiation of Phase II Trial of ADCETRIS® (Brentuximab Vedotin) in Combination with Current Standard of Care for Frontline Diffuse Large B-Cell Lymphoma (DLBCL)
Seattle Genetics, Inc. announced the initiation of a Phase II clinical trial evaluating ADCETRIS in combination with RCHOP (A+RCHOP), the current standard frontline therapy, for newly diagnosed patients with DLBCL. The study is intended to evaluate the complete remission rate and safety of the A+RCHOP regimen. ADCETRIS is an antibody-drug conjugate directed to CD30. [Seattle Genetics, Inc.] Press Release

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Research Scientist – Immune System Signaling (University of Pennsylvania)

Tenure-Track Position – Cell Biologist (McGill University)

Postdoctoral Scientist – Regulatory Activities of B Cells in Infectious and Autoimmune Diseases (Deutsches Rheuma-Forschungszentrum Berlin)

Postdoctoral Position – Innate Immune Signaling in the Developing Intestine (University of Connecticut Health Center)

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

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)

Director of Cell Processing Facility (S L Collins Associates, Inc.)

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

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