Immune Regulation News Volume 6.36 | Sept 26 2014

Dendritic Cell-Bound IgE Functions to Restrain Allergic Inflammation at Mucosal Sites
Investigators show that humanized mice that express FcεRI on dendritic cells (DCs) carry immunoglobulin E (IgE) like non-allergic humans and do not develop spontaneous allergies. Antigen-specific IgE/FcεRI cross-linking fails to induce maturation or production of inflammatory mediators in human DCs and FcεRI-humanized DCs. [Mucosal Immunol] Abstract

Aberrant Presentation of Self-Lipids by Autoimmune B Cells Depletes Peripheral iNKT Cells
Researchers found peripheral, but not thymic, invariant natural killer T (iNKT) cells to be numerically reduced in autoimmune mice lacking Fas specifically in B cells. The residual iNKT cells were antigenically overstimulated, had altered cytokine production, and manifested enhanced proliferation and apoptosis. [Cell Rep]
Full Article | Graphical Abstract | Press Release

Activation of the Arylhydrocarbon Receptor Causes Immunosuppression Primarily by Modulating Dendritic Cells
Investigators identified the arylhydrocarbon receptor (AhR) as a molecular target for ultraviolet radiation (UVR) and its activation to be involved in UVR-induced immunosuppression. Accordingly, the AhR agonist 4-n-nonylphenol suppressed sensitization and induced regulatory T cells similar to UVR. [J Invest Dermatol] Abstract

The NF-κB Regulator Bcl-3 Governs Dendritic Cell Antigen Presentation Functions in Adaptive Immunity
Scientists demonstrate that Bcl-3 is required in dendritic cells (DCs) to assure effective priming of CD4 and CD8 T cells. Lack of Bcl-3 in bone marrow-derived DCs blunted their ability to expand and promote effector functions of T cells upon Ag/adjuvant challenge in vitro and after adoptive transfers in vivo. [J Immunol] Abstract

Opposing Effects of CTLA4 Insufficiency on Regulatory versus Conventional T Cells in Autoimmunity Converge on Effector Memory in Target Tissue
Reduction in CTLA4 levels had an unanticipated effect in promoting regulatory T cells (T_reg) function both in vivo and in vitro. It led to an increase in T_reg memory in both lymphoid and nonlymphoid target tissue. Conversely, modulating CTLA4 by either RNA interference or Ab blockade promoted conventional effector memory T cell formation in the conventional T compartment. [J Immunol] Abstract

Macrophage Deficiency of Akt2 Reduces Atherosclerosis in LDLR Null Mice
Macrophages express three Akt isoforms Akt1, Akt2 and Akt3 but the roles of Akt1 and Akt2 in atherosclerosis in vivo remain unclear. To dissect the impact of macrophage Akt1 and Akt2 on early atherosclerosis, investigators generated mice with hematopoietic deficiency of Akt1 or Akt2. [J Lipid Res] Abstract | Full Article

Dectin-1-Mediated Signaling Leads to Characteristic Gene Expressions and Cytokine Secretion via Syk in Rat Mast Cells
Dectin-1 recognizes β-glucan and plays important roles for the anti-fungal immunity through the activation of Syk in dendritic cells or macrophages. Researchers analyzed rat mast cell line RBL-2H3 to investigate the molecular mechanism of Dectin-1-mediated activation and responses of mast cells. [J Biol Chem]
Abstract | Full Article

Signal Regulatory Protein Alpha (SIRPα) Regulates the Homeostasis of CD103⁺CD11b⁺ DCs in the Intestinal Lamina Propria
The authors demonstrate a role for SIRPα in the homeostasis of CD103⁺CD11b⁺ DCs in the intestine, as well as providing further evidence that this subset of DCs is critical for the development of mucosal T_H17 responses. Loss of SIRPα signaling in mice leads to a selective reduction in the CD103⁺CD11b⁺ subset of DCs in small intestine, colon and amongst migratory DCs in mesenteric lymph node. [Eur J Immunol] Abstract

FoxO3 Is a Negative Regulator of Primary CD8⁺ T-Cell Expansion but Not of Memory Formation
Scientists evaluated the involvement of FoxO3 in the CD8⁺ T-cell response. They observed that CD8⁺ T cells deficient for FoxO3 undergo a significantly greater primary expansion than their wild-type counterparts in response to both infectious (vaccinia virus) or non-infectious (non-replicating cellular vaccine) immunogens, resulting in a larger cohort of cells following contraction. [Immunol Cell Biol] Abstract

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Mast Cells and Basophils in Cutaneous Immune Responses
The authors discuss the recent advances related to mast cells and basophils in human and murine cutaneous immune responses. [Allergy] Abstract | Full Article

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Medigene AG: New Research Collaborations and Additional Grant for Immunotherapy TABs
Medigene AG announces that its subsidiary Trianta Immunotherapies GmbH entered two new research collaborations for further development of its immunotherapy platform TABs (T-cell-specific AntiBodies) for the treatment of various types of cancer and autoimmune diseases. [Medigene AG] Press Release

UC San Diego Part of New Effort to Fight Autoimmune Disorders
The Division of Rheumatology, Allergy and Immunology at University of California, San Diego (UC San Diego) School of Medicine has been named a key site in a national, multi-institution, multi-year $41.6 million program to speed drug discovery, development, diagnostics and therapies for patients with autoimmune disorders, primarily rheumatoid arthritis and lupus erythematosus. [University of California, San Diego] Press Release

Scripps Research Institute Scientists Awarded $7.9 Million to Develop Artificial Immune System
Scientists from both campuses of the Scripps Research Institute have been awarded a total of $7.9 million from the Defense Advanced Research Projects Agency of the U.S. Department of Defense. The two teams will build what is, in essence, an artificial immune system, comprising vast “libraries” of different types of molecules from which will emerge individual compounds to detect or neutralize an array of biological and chemical threats.
[The Scripps Research Institute] Press Release

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