LL37 alone and in complex with self-DNA triggers inflammatory responses in myeloid cells and plays a crucial role in the development of systemic autoimmune diseases, like psoriasis and systemic lupus erythematosus. We demonstrated that LL37/self-DNA complexes induce long-term metabolic and epigenetic changes in monocytes, enhancing their responsiveness to subsequent stimuli. Monocytes trained with LL37/self-DNA complexes and those derived from psoriatic patients exhibited heightened glycolytic and oxidative phosphorylation rates, elevated release of proinflammatory cytokines, and affected naïve CD4 T cells.
View Article and Find Full Text PDFGlioblastoma (GB) is notoriously resistant to therapy. GB genesis and progression are driven by glioblastoma stem-like cells (GSCs). One goal for improving treatment efficacy and patient outcomes is targeting GSCs.
View Article and Find Full Text PDFAutologous platelet concentrates, like liquid platelet rich fibrin (iPRF), optimize wound healing; however, the underlying immunological mechanisms are poorly understood. Platelets, the main cellular component of iPRF, highly express the protein, Glycoprotein A repetitions predominant (GARP), on their surfaces. GARP plays a crucial role in maintaining peripheral tolerance, but its influence on the immune capacity of iPRF remains unclear.
View Article and Find Full Text PDFRegulatory T cells (Treg) play a critical role in immune homeostasis by suppressing several aspects of the immune response. Herein, Glycoprotein A repetitions predominant (GARP), the docking receptor for latent transforming growth factor (LTGF-β), which promotes its activation, plays a crucial role in maintaining Treg mediated immune tolerance. After activation, Treg uniquely express GARP on their surfaces.
View Article and Find Full Text PDFThe cellular composition of the tumor microenvironment, including tumor, immune, stromal, and endothelial cells, significantly influences responses to cancer therapies. In this study, we analyzed the impact of oxidative stress, induced by cold atmospheric plasma (CAP), on tumor cells, T cells, and macrophages, which comprise part of the melanoma microenvironment. To accomplish this, cells were grown in different in vitro cell culture models and were treated with varying amounts of CAP.
View Article and Find Full Text PDFBackground: Malignant melanoma is an immunogenic skin cancer with an increasing global incidence. Advanced stages of melanoma have poor prognoses. Currently, there are no reliable parameters to predict a patient's response to immune checkpoint inhibitor (ICI) therapy.
View Article and Find Full Text PDFPeptidyl-prolyl isomerases (PPIases) are enzymes that catalyze the -to- isomerization around proline bonds, allowing proteins to fold into their correct confirmation. Previously, we identified two PPIase enzymes in (PpiB and PrsA) that are involved in the regulation of virulence determinants and have shown that PpiB contributes to virulence in a murine abscess model of infection. Here, we further examine the role of these PPIases in virulence and, in particular, their regulation of hemolytic toxins.
View Article and Find Full Text PDFSmall RNAs (sRNAs) remain an understudied class of regulatory molecules in bacteria in general and in Gram-positive bacteria in particular. In the major human pathogen , hundreds of sRNAs have been identified; however, only a few have been characterized in detail. In this study, we investigate the role of the sRNA Teg41 in virulence.
View Article and Find Full Text PDFMyeloid cells are the most abundant cells in the tumor microenvironment (TME). The tumor recruits and modulates endogenous myeloid cells to tumor-associated macrophages (TAM), dendritic cells (DC), myeloid-derived suppressor cells (MDSC) and neutrophils (TAN), to sustain an immunosuppressive environment. Pathologically overexpressed mediators produced by cancer cells like granulocyte-macrophage colony-stimulating- and vascular endothelial growth factor induce myelopoiesis in the bone marrow.
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