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Cytosolic DNA composition is determined by genomic instability mechanism and regulates dendritic cell-mediated anti-tumor immunity.
Cell Rep
January 2025
Department of Oncology, Cross Cancer Institute, University of Alberta, Edmonton, AB T6G 1Z2, Canada; Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, AB T6G 2R3, Canada. Electronic address:
Patients with colorectal cancers (CRCs) that have microsatellite instability (MSI) (MSI CRCs) face a better prognosis than those with the more common chromosomal instability (CIN) subtype (CIN CRCs) due to improved T cell-mediated anti-tumor immune responses. Previous investigations identified the cytosolic DNA (cyDNA) sensor STING as necessary for chemokine-mediated T cell recruitment in MSI CRCs. Here, we find that cyDNA from MSI CRC cells is inherently more capable of inducing STING activation and improves cytotoxic T cell activation by dendritic cells (DCs).
View Article and Find Full Text PDFSigma1 inhibitor suppression of adaptive immune resistance mechanisms mediated by cancer cell derived extracellular vesicles.
Cancer Biol Ther
December 2025
Department of Pharmacology, Physiology, and Cancer Biology, Thomas Jefferson University, Philadelphia, PA, USA.
Adaptive immune resistance in cancer describes the various mechanisms by which tumors adapt to evade anti-tumor immune responses. IFN-γ induction of programmed death-ligand 1 (PD-L1) was the first defined and validated adaptive immune resistance mechanism. The endoplasmic reticulum (ER) is central to adaptive immune resistance as immune modulatory secreted and integral membrane proteins are dependent on ER.
View Article and Find Full Text PDFGenetic variation in IL-4 activated tissue resident macrophages determines strain-specific synergistic responses to LPS epigenetically.
Nat Commun
January 2025
Type 2 Immunity Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD, USA.
How macrophages in the tissue environment integrate multiple stimuli depends on the genetic background of the host, but this is still poorly understood. We investigate IL-4 activation of male C57BL/6 and BALB/c strain specific in vivo tissue-resident macrophages (TRMs) from the peritoneal cavity. C57BL/6 TRMs are more transcriptionally responsive to IL-4 stimulation, with induced genes associated with more super enhancers, induced enhancers, and topologically associating domains (TAD) boundaries.
View Article and Find Full Text PDFChinese yam polysaccharide induces the differentiation and natural antibody secretion of IgM B cells to prevent Aeromonas hydrophila infection in grass carp.
Int J Biol Macromol
January 2025
National Key Laboratory of Agricultural Microbiology, Hubei Hongshan Laboratory, Engineering Research Center of Green Development for Conventional Aquatic Biological Industry in the Yangtze River Economic Belt, Ministry of Education, College of Fisheries, Huazhong Agricultural University, Wuhan, China; Shenzhen Institute of Nutrition and Health, Huazhong Agricultural University, Wuhan, China; Shenzhen Branch, Guangdong Laboratory for Lingnan Modern Agriculture, Genome Analysis Laboratory of the Ministry of Agriculture, Agricultural Genomics Institute at Shenzhen, Chinese Academy of Agricultural Sciences, Shenzhen, China. Electronic address:
Chinese yam polysaccharide (CYP) is an effective immunostimulant, however, its efficacy in grass carp, an important commercial fish species in Asia, remains untested. Here, our study evaluated the immunostimulatory effects of CYP on IgM B cells in vitro and on humoral immunity and immune defense against Aeromonas hydrophila infection in vivo. In vitro stimulation experiments showed that CYP could induce the secretion of IgM antibodies, because it could stimulate the proliferation and differentiation of head kidney IgM B cells.
View Article and Find Full Text PDFAllergen-induced activation of epithelial P2Y receptors promotes ATP exocytosis and type 2 immunity in airways.
J Allergy Clin Immunol
January 2025
Departments of Animal Science, Integrative Biology and Physiology, University of Minnesota,St. Paul, MN, 55108. Electronic address:
Background: Environmental allergens induce the release of danger signals from the airway epithelium that trigger type 2 immune responses and promote airway inflammation.
Objective: To investigate the role of allergen-stimulated P2Y receptor activation in regulating ATP, IL-33 and DNA release by human bronchial epithelial (hBE) cells and mouse airways.
Methods: hBE cells were exposed to Alternaria alternata extract and secretion of ATP, IL-33 and DNA were studied in vitro.
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