Orchestrated Intron Retention Regulates Normal Granulocyte Differentiation The authors’ bioinformatic analyses of transcriptomic and proteomic data of normal white blood cell differentiation reveal intron retention (IR) as a physiological mechanism of gene expression control. IR regulates the expression of 86 functionally related genes, including those that determine the nuclear shape that is unique to granulocytes. [Cell] Abstract | Graphical Abstract Notch2-Dependent Classical Dendritic Cells Orchestrate Intestinal Immunity to Attaching-and-Effacing Bacterial Pathogens Scientists used genetic techniques to deplete mice of specific subsets of classical dendritic cells (cDCs) and analyzed immunity to the attaching-and-effacing pathogen Citrobacter rodentium. They found that the signaling receptor Notch2 controlled the terminal stage of cDC differentiation. [Nat Immunol] Abstract Nck-Mediated Recruitment of BCAP to the B Cell Antigen Receptor Regulates the PI(3)K-Akt Pathway in B Cells Investigators found that Nck also controlled the phosphatidylinositol-3-OH kinase (PI(3)K)-kinase Akt pathway by recruiting the adaptor BCAP after activation of B cells. [Nat Immunol] Abstract An Interleukin-17-Mediated Paracrine Network Promotes Tumor Resistance to Anti-Angiogenic Therapy Researchers found that tumor-infiltrating T helper type 17 cells and interleukin-17 induced the expression of granulocyte colony-stimulating factor through nuclear factor κB and extracellular-related kinase signaling, leading to immature myeloid-cell mobilization and recruitment into the tumor microenvironment. [Nat Med] Abstract | Press Release Type III TGF-β Receptor Downregulation Generates an Immunotolerant Tumor Microenvironment Using murine models of breast cancer and melanoma, the authors elucidated a tumor immunoevasion mechanism whereby loss of tumor-expressed Type III TGF-β receptor/shed extracellular domain enhanced TGF-β signaling within locoregional DC populations and upregulated both the immunoregulatory enzyme indoleamine 2,3-dioxygenase in plasmacytoid DCs and the CCL22 chemokine in myeloid DCs. [J Clin Invest] Full Article | Press Release Autonomic Dysreflexia Causes Chronic Immune Suppression after Spinal Cord Injury Experimental activation of spinal sympathetic reflexes in spinal cord injury mice (e.g., via colorectal distension) elicits autonomic dysreflexia and exacerbates immune suppression via a mechanism that involves aberrant accumulation of norepinephrine and glucocorticoids. [J Neurosci] Abstract | Press Release Multistage T Cell-Dendritic Cell Interactions Control Optimal CD4 T Cell Activation through the ADAP-Src Kinase-Associated Phosphoprotein of 55 kDa- Signaling Module Using two-photon microscopy, scientists demonstrated that, in the absence of adhesion and degranulation promoting adapter protein (ADAP), CD4 T cells make fewer early-stage stable contacts with Ag-laden dendritic cells, and the interactions are characterized by brief repetitive contacts. [J Immunol] Abstract Serine Protease Inhibitor 6 Plays a Critical Role in Protecting Murine Granzyme B-Producing Regulatory T Cells The authors showed for the first time that both induced regulatory T cells (Tregs) and natural Tregs increase their intracellular expression of granzyme-B and its endogenous inhibitor, serine protease inhibitor 6 upon activation. [J Immunol] Abstract Regulatory T Cells Prevent Th2 Immune Responses and Pulmonary Eosinophilia during RSV Infection in Mice Investigators used the Foxp3DTR mice (that allow specific conditional depletion of Foxp3+ T cells) to investigate the functional effects of regulatory T cells during A2 strain respiratory syncytial virus (RSV) infection. [J Virol] Abstract Inhibition of the Differentiation of Monocyte-Derived Dendritic Cells by Human Gingival Fibroblasts Researchers investigated whether gingival fibroblasts can modulate the differentiation and/or maturation of monocyte-derived dendritic cells and analyzed soluble factors that may be involved in this immune modulation. [PLoS One] Full Article
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