Intestinal Monocytes and Macrophages Are Required for T Cell Polarization in Response to Citrobacter rodentium Scientists describe a two-gene approach that requires overlapping expression of LysM and Csf1r to define and deplete monocytes and macrophages. The role of monocytes and macrophages in immunity to pathogens was tested by their selective depletion during infection with Citrobacter rodentium. [J Exp Med] Abstract Inhibiting Glycolytic Metabolism Enhances CD8+ T Cell Memory and Antitumor Function The authors used a fluorescent glucose analog, 2-NBDG, to quantify glucose uptake in activated CD8+ T cells. They found that cells exhibiting limited glucose incorporation had a molecular profile characteristic of memory precursor cells and an increased capacity to enter the memory pool compared with cells taking up high amounts of glucose. [J Clin Invest] Full Article | Press Release Targeted Delivery of Proapoptotic Peptides to Tumor-Associated Macrophages Improves Survival Investigators report the discovery of a unique peptide sequence, M2pep, identified using a subtractive phage biopanning strategy against whole cells. The peptide preferentially binds to murine M2 cells, including tumor-associated macrophages, with low affinity for other leukocytes. [Proc Natl Acad Sci USA] Abstract | Press Release Interruption of Dendritic Cell-Mediated TIM-4 Signaling Induces Regulatory T Cells and Promotes Skin Allograft Survival Scientists demonstrated that Ab blockade of dendritic cell-expressed TIM-4 leads to increased induction of induced regulatory T cells (iTregs) from naive CD4+ T cells, both in vitro and in vivo. iTreg induction occurs through suppression of IL-4/STAT6/Gata3-induced Th2 differentiation. [J Immunol] Abstract EGFR Inhibitors Augment Antitumour Helper T-Cell Responses of HER Family-Specific Immunotherapy Investigators report human epidermal receptor (HER) family epitopes that induced CD4 T-cell responses to head and neck squamous cell carcinoma (HNSCC). The results provide support for a novel strategy to treat HNSCC by combining epidermal growth factor receptor (EGFR)-targeted therapy with T-cell-based immunotherapy. [Brit J Cancer] Abstract TLR7 Signaling Exacerbates CNS Autoimmunity through Downregulation of Foxp3+ Treg Cells To define the contribution of Toll-like receptor 7 (TLR7) to the development of autoimmune encephalomyelitis, researchers evaluated the course of the disease in C57BL/6-Tlr7-deficient mice compared with that in wild type mice and found that TLR7-deficient mice had decreased disease severity. This protection was associated with decreased myelin oligodendrocyte glycoprotein-specific T-cell activation by primed dendritic cells, increased Foxp3+ regulatory T (Treg) cells in the periphery, decreased circulating autoantibodies, and attenuated inflammation within the central nervous system (CNS). [Eur J Immunol] Abstract Mechanistic Model of Natural Killer Cell Proliferative Response to IL-15 Receptor Stimulation Researchers developed a mathematical model to analyze the kinetic interactions that control the formation and localization of IL-15/IL-15R complexes. Their computational results demonstrated that IL-15/IL-15 receptor complexes on the cell surface were a key determinant of the magnitude of the IL-15 proliferative signal and that IL-15R occupancy functioned as an effective surrogate measure of receptor signaling. [PLoS Comput Biol] Full Article IL-15 cis Presentation Is Required for Optimal NK Cell Activation in Lipopolysaccharide-Mediated Inflammatory Conditions The authors showed that upon lipopolysaccharide or E. coli exposure, dendritic cells (DCs) produce three cytokines interleukin 2 (IL-2), IL-18, and interferon β (IFN-β) necessary and sufficient for natural killer (NK) cell activation. IFN-β enhances NK cell activation by inducing IL-15 and IL-15 receptor α not only in DCs but, surprisingly, also in NK cells. [Cell Rep] Abstract | Graphical Abstract | Full Article
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