Genome-Derived Cytosolic DNA Mediates Type I Interferon-Dependent Rejection of B Cell Lymphoma Cells
| Autor: | Yu J. Shen, Muznah Khatoo, Nina Le Bert, Christine Xing’Er Koo, Samantha S.W. Ho, Stephan Gasser, Xing H. Nga, Anuja Chitre, Ken Ishii, Nikki Y. Tan |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Adoptive cell transfer
Lymphoma B-Cell DNA damage Mitochondrion Biology Real-Time Polymerase Chain Reaction General Biochemistry Genetics and Molecular Biology Cell Line Mice chemistry.chemical_compound Cytosol Interferon medicine Animals Humans lcsh:QH301-705.5 Genetics Microscopy Confocal Innate immune system DNA HCT116 Cells Adoptive Transfer Cell biology Mice Inbred C57BL Real-time polymerase chain reaction chemistry lcsh:Biology (General) Cell culture Interferon Type I DNA Damage medicine.drug |
| Zdroj: | Cell Reports, Vol 11, Iss 3, Pp 460-473 (2015) |
| ISSN: | 2211-1247 |
| Popis: | SummaryThe DNA damage response (DDR) induces the expression of type I interferons (IFNs), but the underlying mechanisms are poorly understood. Here, we show the presence of cytosolic DNA in different mouse and human tumor cells. Treatment of cells with genotoxic agents increased the levels of cytosolic DNA in a DDR-dependent manner. Cloning of cytosolic DNA molecules from mouse lymphoma cells suggests that cytosolic DNA is derived from unique genomic loci and has the potential to form non-B DNA structures, including R-loops. Overexpression of Rnaseh1, which resolves R-loops, reduced the levels of cytosolic DNA, type I Ifn transcripts, and type I IFN-dependent rejection of lymphoma cells. Live-cell imaging showed a dynamic contact of cytosolic DNA with mitochondria, an important organelle for innate immune recognition of cytosolic nucleotides. In summary, we found that cytosolic DNA is present in many tumor cells and contributes to the immunogenicity of tumor cells. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|