Abstract
Irradiated tissues engage the immune system on many levels. The general assumption is that the initial damage alerts immune cells through universal danger sensing and signaling pathways that are pro-oxidant, pro-inflammatory at first, before morphing into an anti-oxidant, anti-inflammatory counter response. The perpetuating nature of the inflammatory forces that drive normal tissue toxicity seems to originate in part from cytosolic damaged DNA structures that directly and persistently activate innate immune cells, enforce senescence and feed back to the bone marrow, preferentially driving myelopoiesis and further immune activation. Many of the lasting radiation effects on the immune system resemble those seen in premature aging, and are seen in A-bomb survivor studies and amongst bone marrow transplant recipients. These include enhanced T cell senescence, a shrinking T cell repertoire, less T cell functionality, and overall a more pro-inflammatory immune outlook. The ultimate long-term effects also resemble failed attempts at regeneration with fibrosis, scarring, failure of tissue function, and possibly carcinogenesis and are a de facto multi-organ disease. Whether or not the dose response follows a linear, no-threshold low dose dependency, is less clear but it is reasonable to assume that different thresholds exist for different radiation-induced effects. For example, there is evidence that DNA damage that might be repaired at higher doses, at low doses may leave foci of unrepaired lesions on the balance sheet, which may serve as a nidus for a carcinogenic event or as a chronic low-dose stimulus. So, the potential for longer term, chronic low-grade responses may remain, with the possibility of its later amplification by a secondary event such as an infection or wounding. The status of immune activation at the time of radiation exposure, i.e. acute antigen exposure, immune cell activation, differentiation, metabolic and redox balance, proteasome status, and NFκB/Nrf2 activity will hugely affect the net-outcome of low dose radiation events. Understanding how the immune rheostat might be reprogrammed by low dose radiation, the importance of radiation dose, dose rate, and quality, as well as the impact of collateral signals in the context of danger or non-danger signaling is relevant to many life shortening and carcinogenetic events.
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Schaue, D., Iwamoto, K.S., McBride, W.H. (2022). Immune Networks in the Context of Low Dose Ionizing Radiation. In: Wood, M.D., Mothersill, C.E., Tsakanova, G., Cresswell, T., Woloschak, G.E. (eds) Biomarkers of Radiation in the Environment. NATO Science for Peace and Security Series A: Chemistry and Biology. Springer, Dordrecht. https://doi.org/10.1007/978-94-024-2101-9_6
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