Immune Regulation News Volume 7.11 | Mar 27 2015

Local Triggering of the ICOS Coreceptor by CD11c⁺ Myeloid Cells Drives Organ Inflammation in Lupus
Researchers showed that selective ablation of inducible T cell costimulator ligand (ICOSL) in CD11c⁺ cells, but not in B cells, dramatically ameliorated kidney and lung inflammation in lupus-prone MRL.Fas^lpr mice. Autoantibody formation was largely unaffected by ICOSL deficiency in CD11c⁺ cells. [Immunity] Abstract

A Dynamic Spectrum of Monocytes Arising from the In Situ Reprogramming of CCR2⁺ Monocytes at a Site of Sterile Injury
Using spinning-disk confocal intravital microscopy, scientists were able to track the dynamic spectrum of monocytes that enter a site of sterile hepatic injury in vivo. These monocytes transitioned, in situ, from CCR2^hiCx₃CR1^low to CX₃CR1^hiCCR2^low within the ringlike structure and then entered the injury site. [J Exp Med] Abstract

Myeloid Cell-Derived ​Inducible Nitric Oxide Synthase Suppresses M1 Macrophage Polarization
Researchers showed that ​inducible nitric oxide synthase (NOS)-deficient mice displayed enhanced classically activated M1 macrophage polarization without major effects on alternatively activated M2 macrophages. ​Endothelial NOS and ​​neuronal NOS mutant mice showed comparable M1 macrophage polarization compared with wild-type control mice. [Nat Commun] Full Article

Orphan Receptor ​IL-17RD Regulates Toll-Like Receptor Signaling via SEFIR/TIR Interactions
Researchers describe a role for the orphan receptor ​interleukin-17 receptor D (​IL-17RD) in negatively regulating Toll-like receptor (TLR)-induced responses. Deficiency of ​IL-17RD expression in cells leads to enhanced pro-inflammatory signaling and gene expression in response to TLR stimulation, and ​Il17rd^−/− mice are more susceptible to TLR-induced septic shock. [Nat Commun] Abstract

Dynamin 2-Dependent Endocytosis Sustains T-Cell Receptor Signaling and Drives Metabolic Reprogramming in T Lymphocytes
Using genetic inhibition of endocytosis, scientists showed that T-cell receptor (TCR) internalization promoted continued TCR signaling and T-lymphocyte proliferation. T-cell-specific deletion of dynamin 2, an essential component of endocytosis, resulted in reduced TCR signaling strength, impaired homeostatic proliferation, and the inability to undergo clonal expansion in vivo. [Proc Natl Acad Sci USA] Abstract

Age-Associated Inflammation Connects RAS-Induced Senescence to Stem Cell Dysfunction and Epidermal Malignancy
Investigators showed that mutant H-Ras activation in mouse epidermis, a frequent event in cutaneous squamous cell carcinoma, elicits a differential outcome in aged versus young mice. Progression was associated with increased inflammation, pronounced accumulation of immune cells including T cells, macrophages and mast cells as well as excessive cell senescence. [Cell Death Dis] Abstract

Antigen Design Enhances the Immunogenicity of Semliki Forest Virus-Based Therapeutic Human Papillomavirus Vaccines
Scientists generated, characterized and evaluated the efficacy of recombinant Semliki Forest virus replicon particles expressing human papillomavirus E6 and/or E7 proteins fused to several helper T-cell epitopes and an ER targeting signal. They showed that inclusion of a helper cassette and an ER targeting signal enhanced protein stability and markedly augmented the frequencies of human papillomavirus-specific T cells. [Gene Ther] Abstract

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Taconic Biosciences and Cellaria Biosciences Agree to Scientific Collaboration to Facilitate Xenograft Use in Oncology Research
Taconic Biosciences and Cellaria Biosciences announced that the two companies have entered into a scientific collaboration designed to facilitate and improve the utility of patient-derived xenografts in animal models for oncology and immuno-oncology research. [Taconic Biosciences, Inc.] Press Release

Sanofi Pasteur Announces FDA Approval of Quadracel DTaP-IPV Vaccine for Children Four through Six Years of Age
Sanofi Pasteur announced that the U.S. Food and Drug Administration (FDA) has approved use of Quadracel™ vaccine for active immunization against diphtheria, tetanus, pertussis and poliomyelitis in children four through six years of age. [Sanofi Pasteur SA] Press Release

THERAVECTYS Granted Authorization by the French National Agency for Medicines to Produce Lentiviral Vectors for Clinical Use and CAR-T Cell Therapies under GMP Standards
THERAVECTYS announced that its manufacturing plant has been granted the status of a GMP pharmaceutical manufacturing establishment, by the French National Agency for Medicines and Health Products Safety. [THERAVECTYS] Press Release

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