T Cells Engineered against a Native Antigen Can Surmount Immunologic and Physical Barriers to Treat Pancreatic Ductal Adenocarcinoma Investigators tested the ability of T cells engineered to express an affinity-enhanced T cell receptor against a native antigen to overcome these barriers in a genetically engineered model of autochthonous pancreatic ductal adenocarcinoma. [Cancer Cell] Abstract | Graphical Abstract | Press Release Perforin-Positive Dendritic Cells Exhibit an Immuno-Regulatory Role in Metabolic Syndrome and Autoimmunity Researchers showed the regulatory impact of a rare subpopulation of dendritic cells, rich in perforin-containing granules (perf-DCs). Using bone marrow transplantation to generate animals selectively lacking perf-DCs, they found that these chimeras progressively gained weight and exhibited features of metabolic syndrome. [Immunity] Abstract | Graphical Abstract | Press Release IL-2Rα Mediates Temporal Regulation of IL-2 Signaling and Enhances Immunotherapy Scientists demonstrated that although interleukin (IL)-15 may be effective in lymphopenic patients, IL-2 therapy may be needed in patients who retain immune cells, where T cells compete for available cytokine. They showed that IL-2 but not IL-15 can sustain signaling after cytokine withdrawal through its high-affinity receptor subunit IL-2Rα. [Sci Transl Med] Abstract CCR2 Defines In Vivo Development and Homing of IL-23-Driven GM-CSF-Producing Th17 Cells Researchers identified a temporally regulated IL-23-dependent switch from CCR6 to CCR2 usage by developing IL-17-producing helper T (Th17) cells that is critical for pathogenic Th17 cell-driven inflammation in experimental autoimmune encephalomyelitis. [Nat Commun] Full Article | Press Release RNA Sensing by Conventional Dendritic Cells Is Central to the Development of Lupus Nephritis Researchers showed that conventional dendritic cell (DC) expression of Toll-like receptor 7 is essential for severe autoimmunity in the Sle1Tg7 model of systemic lupus erythematosus. They showed that a novel expanding CD11b+ conventional DC subpopulation dominates the infiltrating renal inflammatory milieu, localizing to the glomeruli. [Proc Natl Acad Sci USA] Abstract Trans-Presentation of IL-15 Modulates STAT5 Activation and Bcl-6 Expression in TH1 Cells Scientists demonstrated that differentiated TH1 cells are responsive to trans-presented IL-15. Importantly, while trans-presentation of IL-15 results in STAT5 activation and maintenance of the TH1 gene program, IL-15 treatment alone allows for increased Bcl-6 expression and the upregulation of a TFH-like profile. [Sci Rep] Full Article | Press Release Apoptosis of Tumor Infiltrating Effector TIM-3+CD8+ T Cells in Colon Cancer The authors report apoptosis of IFN-γ competent TIM-3+ population of tumor-infiltrating CD8+ T cells in colon cancer. In mouse CT26 colon tumor model, majority of tumor-infiltrating CD8+ T cells express TIM-3 and execute cytolysis function with higher effector cytokine secretion and apoptosis in TIM-3+ compared to TIM-3– population. [Sci Rep] Full Article Modulation of Innate Immune Responses via Covalently Linked TLR Agonists Scientists synthesized combinations of Toll-like receptor (TLR) agonists as spatially defined tri- and di-agonists to understand how specific TLR agonist combinations contribute to the overall immune response. [ACS Cent Sci] Full Article | Press Release Don’t forget to subscribe to Human Immunology News and Immunology of Infectious Disease News! |