Low dose ionizing radiation and the immune response: what is the role of non-targeted effects?

Abstract

Objectives

This review aims to trace the historical narrative surrounding the low dose effects of radiation on the immune system and how our understanding has changed from the beginning of the 20th century to now. The particular focus is on the non-targeted effects (NTEs) of low dose ionizing radiation (LDIR) which are effects that occur when irradiated cells emit signals that cause effects in the nearby or distant non-irradiated cells known as radiation induced bystander effect (RIBE). Moreover, radiation induced genomic instability (RIGI) and abscopal effect (AE) also regarded as NTE. This was prompted by our recent discovery that ultraviolet A (UVA) photons are emitted by the irradiated cells and that these photons can trigger NTE such as the RIBE in unirradiated recipients of these photons. Given the well-known association between UV radiation and the immune response, where these biophotons may pose as bystander signals potentiating processes in deep tissues as a consequence of LDIR, it is timely to review the field with a fresh lens. Various pathways and immune components that contribute to the beneficial and adverse types of modulation induced by LDR will also be revisited.

Conclusion

There is limited evidence for LDIR induced immune effects by way of a non-targeted mechanism in biological tissue. The literature examining low to medium dose effects of ionizing radiation on the immune system and its components is complex and controversial. Early work was compromised by lack of good dosimetry while later work mainly looks at the involvement of immune response in radiotherapy. There is a lack of research in the LDIR/NTE field focusing on immune response although bone marrow stem cells and lineages were critical in the identification and characterization of NTE where effects like RIGI and RIBE were heavily researched. This may be in part, a result of the difficulty of isolating NTE in whole organisms which are essential for good immune response studies. Models involving inter organism transmission of NTE are a promising route to overcome these issues.

Keywords:

• Low dose ionizing radiation
• bystander effects
• immune responses
• genomic instability
• adaptive response to radiation

Acknowledgments

We thank National Chronic Fatigue and Immunodeficiency Syndrome (CFIDS) Foundation Inc, for supporting this work. Additionally, I extend my appreciation to Irfan Ahmad Siddiqui who helped with the graphics.

Disclosure statement

The authors declare no conflicts of interest.

Additional information

Funding

This work was funded by our CRD (Collaborative Research and Development) with NSERC and COG as partners. Grant # CRDPJ 484381 - 15.

Notes on contributors

Annum Dawood

Annum Dawood is an MSc. Candidate in the program of Radiation Biology administered through the Department of Physics and Astronomy, McMaster University, Hamilton, ON, Canada. She is also a registered Medical Radiation Technologist (MRT) practicing in the province of Ontario.

Carmel Mothersill

Carmel Mothersill is a Professor of Radiation Biology at McMaster University interested in the impacts of low dose and chronic radiation exposures on non-human species and on ecosystems.

Colin Seymour

Colin Seymour is a Professor of Radiation Biology at McMaster University interested in the biological consequences of low-level radiation exposure.