The Nlrp3 Inflammasome Suppresses Colorectal Cancer Metastatic Growth in the Liver by Promoting Natural Killer Cell Tumoricidal Activity Investigators showed that mice deficient in Nlrp3 inflammasome components had exacerbated liver colorectal cancer metastatic growth, which was mediated by impaired inteleukin-18 (IL-18) signaling. The inflammasome-IL-18 pathway impacted maturation of hepatic NK cells, surface expression of the death ligand FasL, and capacity to kill FasL-sensitive tumors. [Immunity] Abstract | Graphical Abstract | Press Release Perforin-Positive Dendritic Cells Exhibit an Immuno-Regulatory Role in Metabolic Syndrome and Autoimmunity Using bone marrow transplantation to generate animals selectively lacking dendritic cells rich in perforin-containing granules, researchers found that these chimeras progressively gained weight and exhibited features of metabolic syndrome. This phenotype was associated with an altered repertoire of T cells residing in adipose tissue and could be completely prevented by T cell depletion in vivo. [Immunity] Full Article | Graphical Abstract | Press Release Inhibition of Hyaluronan Synthesis Restores Immune Tolerance during Autoimmune Insulitis Scientists demonstrated that hyaluronan (HA) is critical for the pathogenesis of autoimmune diabetes. An inhibitor of HA synthesis, 4-methylumbelliferone, reduced HA accumulation, constrained effector T cells to nondestructive insulitis, and increased numbers of intraislet FOXP3+ Tregs. [J Clin Invest] Full Article | Press Release GITR Subverts Foxp3+ Tregs to Boost Th9 Immunity through Regulation of Histone Acetylation Researchers demonstrated that glucocorticoid-induced TNFR-related protein (GITR) ligation subverts the induction of Foxp3+ regulatory T cells (Tregs) and directs the activated CD4+ T cells to Th9 cells. Such GITR-mediated iTreg to Th9 induction enhances anti-tumor immunity in vivo. [Nat Commun] Full Article | Press Release Regulation of NKT Cell-Mediated Immune Responses to Tumors and Liver Inflammation by Mitochondrial PGAM5-Drp1 Signaling Researchers demonstrated that receptor-interacting protein kinase 3 (RIPK3) plays an essential role in natural killer T (NKT) cell function via activation of the mitochondrial phosphatase phosphoglycerate mutase 5 (PGAM5). RIPK3-mediated activation of PGAM5 promotes the expression of cytokines by facilitating nuclear translocation of NFAT and dephosphorylation of dynamin-related protein 1. [Nat Commun] Full Article | Press Release The B-Cell Antigen Receptor Integrates Adaptive and Innate Immune Signals Scientists showed that the proliferative response of B cells to the latter stimuli is controlled by B-cell antigen receptor-dependent activation of phosphoinositidyl 3-kinase signaling. [Proc Natl Acad Sci USA] Abstract | Full Article Signal Strength Regulates Antigen-Mediated T-Cell Deceleration by Distinct Mechanisms to Promote Local Exploration or Arrest The authors report that high-affinity antigen induced a pronounced deceleration selectively dependent on Ca2+ signals and actin-related protein 2/3 complex activity. In contrast, low-affinity antigens induced a switch of migration mode that promotes T-cell exploratory behavior, characterized by partial deceleration and frequent direction changes. [Proc Natl Acad Sci USA] Abstract | Full Article Copy Number Variations of HLA-I and Activation of NKp30 Pathway Determine the Sensitivity of Gastric Cancer Cells to the Cytotoxicity of Natural Killer Cells Researchers found that the tumorigenic capacity of human gastric cancer (GC) cell lines was dependent on the recruitment and activation of natural killer (NK) cells in xenograft tumors. They used whole-genome sequence on GC cell lines to identify potential genes controlling susceptibility to NK-mediated killing. [Oncogene] Abstract CD4 T Cells Are Required for Both Development and Maintenance of Disease in a New Mouse Model of Reversible Colitis Scientists developed a new model of reversible colitis in which adoptive transfer of CD4+CD45RBhi T cells into Helicobacter typhlonius–colonized lymphopenic mice resulted in a rapid onset of colonic inflammation that was reversible through depletion of colitogenic T cells. Colitogenic T cells were not only critical for induction of colitis but also for maintenance of disease. [Mucosal Immunol] Abstract CD8+NKT-Like Cells Regulate the Immune Response by Killing Antigen-Bearing DCs The authors report that CD1d-independent CD8+NKT-like cells, which express both T cell markers and NK cell receptors, are activated and significantly expanded in mice immunized with GFP-expressing dendritic cells (DCs). [Sci Rep] Full Article Don’t forget to subscribe to Human Immunology News and Immunology of Infectious Disease News! |