T Cells Contribute to Pathological Responses in the Non-Targeted Rat Heart following Irradiation of the Kidneys. Toxics 2022 Dec 18;10(12)
Date
12/23/2022Pubmed ID
36548630Pubmed Central ID
PMC9783591DOI
10.3390/toxics10120797Abstract
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.
Author List
Lenarczyk M, Alsheikh AJ, Cohen EP, Schaue D, Kronenberg A, Geurts A, Klawikowski S, Mattson D, Baker JEAuthors
John E. Baker PhD Professor in the Surgery department at Medical College of WisconsinAron Geurts PhD Professor in the Physiology department at Medical College of Wisconsin
