T Cells Become Licensed in the Lung to Enter the Central Nervous System In the autoimmune disease multiple sclerosis, myelin-reactive T-cell blasts are thought to transgress the blood-brain barrier (BBB) and create a pro-inflammatory environment in the central nervous system (CNS), thereby making possible a second autoimmune attack that starts from the leptomeningeal vessels and progresses into the parenchyma. Using a Lewis rat model of experimental autoimmune encephalomyelitis, researchers showed that contrary to the expectations of this concept, T-cell blasts do not efficiently enter the CNS and are not required to prepare the BBB for immune-cell recruitment. [Nature] Abstract Acute Gastrointestinal Infection Induces Long-Lived Microbiota-Specific T Cell Responses The authors showed that during a gastrointestinal infection, tolerance to commensals is lost and microbiota-specific T cells are activated and differentiate to inflammatory effector cells. Furthermore, these T cells go on to form memory cells that are phenotypically and functionally consistent with pathogen-specific T cells. [Science] Abstract Interleukin-22 Protects Intestinal Stem Cells from Immune-Mediated Tissue Damage and Regulates Sensitivity to Graft versus Host Disease Researchers demonstrated that deficiency of recipient-derived interleukin (IL)-22 increased acute graft versus host disease (GvHD) tissue damage and mortality, that intestinal stem cells were eliminated during GvHD, and that intestinal stem cells as well as their downstream progenitors expressed the IL-22 receptor. [Immunity] Abstract A Broad Range of Self-Reactivity Drives Thymic Regulatory T Cell Selection to Limit Responses to Self Researchers analyzed a panel of T cell receptors (TCRs) with a broad range of reactivity to ovalbumin (OVA323-339) in the rat insulin promoter-mOVA self-antigen model for their ability to trigger thymic self-tolerance mechanisms. Thymic regulatory T cell generation in vivo was directly correlated with in vitro TCR reactivity to OVA-peptide in a broad 1,000-fold range. [Immunity] Abstract Nucleic Acid-Containing Amyloid Fibrils Potently Induce Type I Interferon and Stimulate Systemic Autoimmunity The authors report that nucleic acid-containing amyloid fibrils can potently activate plasmacytoid dendritic cells (pDCs) and enable type I interferon (INF) production in response to self-DNA, self-RNA, and dead cell debris. pDCs can take up DNA-containing amyloid fibrils, which are retained in the early endosomes to activate TLR9, leading to high IFNα/β production. [Proc Natl Acad Sci USA] Abstract The Proinflammatory Myeloid Cell Receptor TREM-1 Controls Kupffer Cell Activation and Development of Hepatocellular Carcinoma Researchers report causal evidence that TREM-1 is a pivotal determinant of Kupffer cell activation in liver carcinogenesis, deepening mechanistic insights into how chronic inflammation underpins the development and progression of liver cancer. [Cancer Res] Abstract | Press Release Plexin-B2 and Plexin-D1 in Dendritic Cells: Expression and IL-12/IL-23p40 Production This is the first report to show an association between Plexin-B2 and Plexin-D1 with the negative regulation of IL-12/IL-23p40 in dendritic cells (DCs). This work also showed the presence of Plexin-B2 and Plexin-D1 on mouse DC subpopulations, and indicated that these two proteins play a role in IL-12/IL-23p40 production that is likely to impact the immune response. [PLoS One] Full Article Improving Dendritic Cell Vaccine Immunogenicity by Silencing PD-1 Ligands Using siRNA-Lipid Nanoparticles Combined with Antigen mRNA Electroporation Researchers explored the generation of a clinical-grade applicable dendritic cell (DC) vaccine with improved immunogenic potential by combining PD-1 ligand siRNA and target antigen mRNA delivery. They demonstrated that PD-L1 and PD-L2 siRNA delivery using DLin-KC2-DMA-containing lipid nanoparticles mediated efficient and specific knockdown of PD-L expression on human monocyte-derived DC. [Cancer Immunol Immunother] Abstract | Press Release |