Journal
PHARMACOLOGY & THERAPEUTICS
Volume 154, Issue -, Pages 36-56Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.pharmthera.2015.06.011
Keywords
DNA damage response and repair machinery; Immune response; Pattern recognition receptors; Inflammation; Cancer; Autoimmunity
Categories
Funding
- European Union (European Social Fund - ESF)
- Greek national funds [379435]
- EU Marie Curie Reintegration Grant - European Union (European Social Fund-ESF) [MC-CIG-303514]
- Greek national funds through the Operational Program Educational and Lifelong Learning of the National Strategic Reference Framework (NSRF) Research Funding Program: THALES [MIS 379346]
- COST Action CM1201 Biomimetic Radical Chemistry
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The characteristic feature of healthy living organisms is the preservation of homeostasis. Compelling evidence highlight that the DNA damage response and repair (DDR/R) and immune response (ImmR) signaling networks work together favoring the harmonized function of (multi)cellular organisms. DNA and RNA viruses activate the DDR/R machinery in the host cells both directly and indirectly. Activation of DDR/R in turn favors the immunogenicity of the incipient cell. Hence, stimulation of DDR/R by exogenous or endogenous insults triggers innate and adaptive ImmR. The immunogenic properties of ionizing radiation, a prototypic DDR/R inducer, serve as suitable examples of how DDR/R stimulation alerts host immunity. Thus, critical cellular danger signals stimulate defense at the systemic level and vice versa. Disruption of DDR/R-ImmR cross talk compromises (multi)cellular integrity, leading to cell-cycle-related and immune defects. The emerging DDR/R-ImmR concept opens up a new avenue of therapeutic options, recalling the Hippocrates quote everything in excess is opposed by nature. (C) 2015 Elsevier Inc. All rights reserved.
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