Immune Regulation News Volume 4.21 | Jun 8 2012

Safety, Activity, and Immune Correlates of Anti-PD-1 Antibody in Cancer
Blockade of programmed death 1 (PD-1), an inhibitory receptor expressed by T cells, can overcome immune resistance. In this study, researchers assessed the antitumor activity and safety of BMS-936558, an antibody that specifically blocks PD-1. [N Engl J Med] Abstract | Full Article | Press Release | Video

Innate Lymphoid Cells Promote Anatomical Containment of Lymphoid-Resident Commensal Bacteria
Researchers present data that indicate that innate lymphoid cells regulate selective containment of lymphoid-resident bacteria to prevent systemic inflammation associated with chronic diseases. [Science]
Abstract | Press Release

Interactions between Commensal Fungi and the C-Type Lectin Receptor Dectin-1 Influence Colitis
The results of this study revealed a eukaryotic fungal community in the gut that coexists with bacteria and substantially expands the repertoire of organisms interacting with the intestinal immune system to influence health and disease. [Science] Abstract | Press Release

Photocrosslinkable pMHC Monomers Stain T Cells Specifically and Cause Ligand-Bound TCRs to Be ‘Preferentially’ Transported to the cSMAC
The binding of T cell antigen receptors (TCRs) to specific complexes of peptide and major histocompatibility complex (pMHC) is typically of very low affinity, which necessitates the use of multimeric pMHC complexes to label T lymphocytes stably. The authors report the development of pMHC complexes able to be crosslinked by ultraviolet irradiation; even as monomers, these efficiently and specifically stained cognate T cells. [Nat Immunol] Abstract

The MicroRNA miR-23b Suppresses Interleukin-17-Associated Autoimmune Inflammation by Targeting TGF-β-Activated Kinase 1/MAP3K7 Binding Protein 2 (TAB2), TAB3 and Inhibitor of Nuclear Factor κ-B Kinase Subunit-α
Researchers showed that miR-23b is downregulated in inflammatory lesions of humans with lupus or rheumatoid arthritis, as well as in the mouse models of lupus, rheumatoid arthritis or multiple sclerosis. [Nat Med] Abstract

Oligodendrocytes Enforce Immune Tolerance of the Uninfected Brain by Purging the Peripheral Repertoire of Autoreactive CD8⁺ T Cells
Myelin-specific CD8⁺ T cells are thought to contribute to the pathogenesis of multiple sclerosis. Researchers modeled this contribution in mice with CD8⁺ T cells recognizing ovalbumin (OVA) expressed in oligodendrocytes. Surprisingly, even very high numbers of activated OVA-reactive CD8⁺ T cells failed to induce disease and were cleared from the immune system after antigen encounter in the central nervous system. [Immunity] Abstract

Dynamic In Situ Cytometry Uncovers T Cell Receptor Signaling during Immunological Synapses and Kinapses In Vivo
Researchers introduced dynamic in situ cytometry, a combination of intravital multiphoton imaging and flow cytometry-like phenotypic analysis. Taking advantage of CD62L shedding as a marker of early T cell receptor (TCR) signaling, they examined how T cells sense TCR ligands of varying affinities in vivo. [Immunity] Abstract

Safety, Tolerability, and Antibody Response of Active Aß Immunotherapy with CAD106 in Patients with Alzheimer’s Disease: Randomized, Double-Blind, Placebo-Controlled, First-in-Human Study
Immunotherapy targeting the amyloid ß (Aß) peptide is a potential strategy to slow the progression of Alzheimer’s disease. In this study, researchers assessed the safety and tolerability of CAD106, a novel active Aß immunotherapy for patients with Alzheimer’s disease, designed to induce N-terminal Aß-specific antibodies without an Aß-specific T-cell response. [Lancet Neurol] Abstract | Press Release

The B-Cell Identity Factor Pax5 Regulates Distinct Transcriptional Programs in Early and Late B Lymphopoiesis
Researchers used genome-wide approaches to identify Pax5 target genes in pro-B and mature B cells. In these cell types, Pax5 bound to 40 percent of the cis-regulatory elements defined by mapping DNase I hypersensitive sites, transcription start sites and histone modifications. [EMBO J] Abstract

SOCS2-Induced Proteasome-Dependent TRAF6 Degradation: A Common Anti-Inflammatory Pathway for Control of Innate Immune Responses
Researchers demonstrated that tumor necrosis factor receptor-associated factor 6 (TRAF6) is targeted by both lipoxins and L-kynurenine via an aryl hydrocarbon receptor/suppressors of cytokine signaling 2 (SOCS2)-dependent pathway. [PLoS One] Full Article

Cancer Immunotherapy Firm Raises $1.5 Million, Eyes Strategic Partners
A company developing products to restore the immune system of cancer patients has raised $1.5 million and is now looking for strategic partners. IRX Therapeutics’ lead product aims to correct dendritic cell and T-cell defects in cancer patients in order to overcome cancer-induced immune suppression and restore antitumor response. [MEDCITY News] Press Release

Ferring Pharmaceuticals Donates $10 Million to the Salk Institute for Biological Studies
In addition to funding the highest scientific priorities at the Salk, the Ferring gift will enable the creation of the Françoise Gilot-Salk endowed Chair, which will be used to support research on the role that TAM receptors play in immune regulation. [Salk Institute for Biological Studies] Press Release

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)

NEW Keystone Symposia on Molecular and Cellular Biology: Type 2 Immunity – Initiation, Maintenance, Homeostasis and Pathology
Santa Fe, United States
January 10-15, 2013

NEW Keystone Symposia on Molecular and Cellular Biology: Emerging Topics in Immune System Plasticity – Cellular Networks, Metabolic Control and Regeneration
Santa Fe, United States
January 15-20, 2013

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