Immune Regulation News Volume 5.15 | Apr 26 2013

Follicular T-Helper Cell Recruitment Governed by Bystander B Cells and ICOS-Driven Motility
The authors showed that inducible co-stimulator (ICOS) directly controls follicular recruitment of activated T-helper cells in mice. This effect is independent from ICOS ligand-mediated co-stimulation provided by antigen-presenting dendritic cells or cognate B cells, and does not rely on Bcl6-mediated programming as an intermediate step. [Nature] Abstract

Cutaneous Immunosurveillance and Regulation of Inflammation by Group 2 Innate Lymphoid Cells
Researchers report the identification in normal mouse dermis of an abundant, phenotypically unique group 2 innate lymphoid cell (ILC2) subset that depended on interleukin 7 (IL-7) and constitutively produced IL-13. Intravital multiphoton microscopy showed that dermal ILC2 cells specifically interacted with mast cells, whose function was suppressed by IL-13. [Nat Immunol] Abstract | Press Release

Intrahepatic Myeloid-Cell Aggregates Enable Local Proliferation of CD8⁺ T Cells and Successful Immunotherapy against Chronic Viral Liver Infection
The authors report that signaling via Toll-like receptors induced intrahepatic aggregates of myeloid cells that enabled the population expansion of cytotoxic T lymphcoytes without causing immunopathology. [Nat Immunol] Abstract | Press Release

Peli1 Promotes Microglia-Mediated CNS Inflammation by Regulating TNF Receptor-Associated Factor 3 Degradation
Investigators showed that the E3 ubiquitin ligase Peli1 is abundantly expressed in microglia and promotes microglial activation during the course of experimental autoimmune encephalomyelitis induction. Peli1 mediates the induction of chemokines and proinflammatory cytokines in microglia and thereby promotes recruitment of T cells into the central nervous system. [Nat Med] Abstract

Tumor Cells in Multiple Myeloma Patients Inhibit Myeloma-Reactive T Cells through Carcinoembryonic-Antigen-Related Cell Adhesion Molecule-6
Scientists demonstrated that cytotoxic T cells reacted against myeloma antigens when presented by autologous dendritic cells, but not by myeloma cells. [Blood] Abstract

Soluble IL7Rα Potentiates IL-7 Bioactivity and Promotes Autoimmunity
Researchers demonstrated that soluble interleukin-7 receptor (sIL7Rα) has moderate affinity for IL-7 but does not bind thymic stromal lymphopoietin. Functionally, sIL7Rα competes with cell-associated IL-7 receptor to diminish excessive IL-7 consumption and, thus, enhances the bioactivity of IL-7 when the cytokine is limited, as it is presumed to be in vivo. [Proc Natl Acad Sci USA] Abstract

Keratinocyte-Specific Deletion of the Receptor RAGE Modulates the Kinetics of Skin Inflammation In Vivo
Using mice harboring a keratinocyte-specific deletion of receptor for advanced glycation end products (RAGE), researchers analyzed its role in the regulation of an acute inflammatory response that was induced by topical treatment of the back skin with the phorbol ester 12-O-tetradecanoyl-phorbol-13-acetate. They showed that RAGE expression in cutaneous keratinocytes modulates the strength and kinetics of acute inflammation, and supports the maintenance of epidermal keratinocyte activation. [J Invest Dermatol] Abstract

IL-17 Stimulates Differentiation of Human Anti-Inflammatory Macrophages and Phagocytosis of Apoptotic Neutrophils in Response to IL-10 and Glucocorticoids
Exposure of human monocytes/macrophages to anti-inflammatory agents, such as IL-10 or glucocorticoids, can lead to two separate fates: either Fas/CD95-mediated apoptosis or differentiation into regulatory and efferocytic CD14^brightCD16⁺CD163⁺Mer tyrosine kinase⁺ macrophages. Researchers found that the prevalent effect depends on the type of Th cytokine environment and on the stage of monocyte-to-macrophage differentiation. [J Immunol] Abstract

Communication between Human Mast Cells and CD4⁺ T Cells through Antigen-Dependent Interactions
To study the T cell-stimulatory potential of human mast cells, CD34⁺ stem cell-derived mast cells were generated. These cells expressed HLA-DR when stimulated with IFN-γ, and, importantly, presented peptide and protein for activation of antigen-specific CD4⁺ T cells. [Eur J Immunol] Abstract

Don’t forget to subscribe to our sister publications: Human Immunology News and Immunology of Infectious Disease News!

Macrophage Biology in Development, Homeostasis and Disease
The authors define the ‘hallmarks’ of macrophages according to the states that they adopt during the performance of their various roles, taking into account new insights into the diversity of their lineages, identities and regulation. [Nature] Abstract

Innate Immunity and Its Regulation by Mast Cells
The authors discuss the evidence supporting the dual role of mast cells, both as sentinels for invading pathogens and as regulatory cells throughout the course of acute inflammation, from its initiation to resolution. [J Immunol] Abstract

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

Arkansas Children’s Hospital Research Institute Scientists Receive $1.3 Million from National Institutes of Health to Study How Pollutant Affects Children’s Developing Immune Systems
Kathleen Gilbert, PhD, and Sarah Blossom, PhD, have received a four-year grant to study how chronic low exposure to trichloroethylene during prenatal, infant and childhood development may contribute to autoimmune diseases like diabetes, lupus and autoimmune hepatitis later in life. [Arkansas Children’s Hospital Research Institute] Press Release

Monoclonal Antibody with Xencor’s High ADCC Fc Technology Enters Phase II Study in B-Cell Acute Lymphoblastic Leukemia
Xencor announced that MorphoSys AG has dosed the first patient in a Phase II clinical trial of MOR208 in B-cell acute lymphoblastic leukemia. MOR208 is a potent anti-CD19 monoclonal antibody Fc optimized for high cytotoxic function for which MorphoSys licensed exclusive worldwide rights from Xencor in 2010. [Xencor, Inc.] Press Release

Merck Announces Breakthrough Therapy Designation for Lambrolizumab an Investigational Antibody Therapy for Advanced Melanoma
Merck announced that the U.S. Food and Drug Administration has designated lambrolizumab as a Breakthrough Therapy for the treatment of patients with advanced melanoma. Lambrolizumab is Merck’s investigational antibody therapy targeting Programmed Death receptor that is currently being evaluated for the treatment of patients with advanced melanoma, and other tumor types. [Merck & Co., Inc.] Press Release

Bioatla Combines Epivax’s Immunogenicity Screening into Their Express Humanization^TM Platform
EpiVax Inc. and BioAtla, LLC announced a collaborative agreement to incorporate EpiVax’ proprietary immunogenicity screening technology into BioAtla’s antibody Express Humanization^TM platform. [EpiVax Inc.] Press Release

From our sponsor: Free Nature Reviews Immunology poster – Immune Response to HIV. Request a copy.

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 43^rd Annual Meeting German Society for Immunology (DGfI)
September 11-14, 2013
Mainz, Germany

Visit our events page to see a complete list of events in the immune regulation community.

NEW PhD Studentship – Treating Metastatic Disease by Manipulation of Regulatory T Cells (Cardiff School of Medicine)

Postdoctoral Fellow – Immunological Pathways in Human Inflammatory Bowel Disease (Yale University – School of Medicine)

PhD Studentship – Mucosal immunology (KU Leuven Translational Research Center for Gastrointestinal Disorders)

Postdoctoral Position – Immunology (Institut Pasteur)

Postdoctoral Position – Immunology (INSERM 1020)

Postdoctoral Fellow – Immunotherapeutics in Childhood Cancer (Perelman School of Medicine at the University of Pennsylvania)

PhD Studentship – Thymic Dendritic Cells and Regulation of T-Cell Development (University of Birmingham / MRC Centre for Immune Regulation)

Recruit Top Talent: Reach more than 50,000 potential candidates by posting your organization’s career opportunities on the Connexon Creative Job Board at no cost.

Have we missed an important article or publication in Immune Regulation News? Click here to submit!

Comments or Suggestions? Email info@connexoncreative.com with your feedback.