Immune Networks in the Context of Low Dose Ionizing Radiation

Schaue, Dörthe; Iwamoto, Keisuke S.; McBride, William H.

doi:10.1007/978-94-024-2101-9_6

Cited by 1 publication

(1 citation statement)

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“…In the setting of non-targeted effects, the heart would receive radiation from out-offield sources; external air scatter originating from the X-ray tube that is independent of distance between anatomical sites and internal low dose X-ray scatter through the rat tissues that is dependent on anatomical distance. Radiation dose will likely be an important determinant in the type and extent of the response as different cellular mechanisms seem to have different thresholds, e.g., micronuclei formation or Nrf2 activation at 20 mGy [20] versus ER stress and proteasome changes at 50 mGy [21] versus ATP release at 100-250 mGy [22,23]. However, direct irradiation of the heart with 10 Gy did not result in pathology [2].…”

Section: Discussionmentioning

confidence: 99%

T Cells Contribute to Pathological Responses in the Non-Targeted Rat Heart following Irradiation of the Kidneys

Lenarczyk

Alsheikh

Cohen

et al. 2022

Toxics

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Heart disease is a significant adverse event caused by radiotherapy for some cancers. Identifying the origins of radiogenic heart disease will allow therapies to be developed. Previous studies showed non-targeted effects manifest as fibrosis in the non-irradiated heart after 120 days following targeted X-irradiation of the kidneys with 10 Gy in WAG/RijCmcr rats. To demonstrate the involvement of T cells in driving pathophysiological responses in the out-of-field heart, and to characterize the timing of immune cell engagement, we created and validated a T cell knock downrat on the WAG genetic backgrou nd. Irradiation of the kidneys with 10 Gy of X-rays in wild-type rats resulted in infiltration of T cells, natural killer cells, and macrophages after 120 days, and none of these after 40 days, suggesting immune cell engagement is a late response. The radiation nephropathy and cardiac fibrosis that resulted in these animals after 120 days was significantly decreased in irradiated T cell depleted rats. We conclude that T cells function as an effector cell in communicating signals from the irradiated kidneys which cause pathologic remodeling of non-targeted heart.

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