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

Lenarczyk, Marek; Alsheikh, Ammar J.; Cohen, Eric P.; Schaue, Dörthe; Kronenberg, Amy; Geurts, Aron; Klawikowski, Slade; Mattson, David; Baker, John E.

doi:10.3390/toxics10120797

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

Journal Article · Sun Dec 18 00:00:00 EST 2022 · Toxics

DOI:https://doi.org/10.3390/toxics10120797· OSTI ID:2470590

Lenarczyk, Marek ^[1]; ^[1]; Cohen, Eric P. ^[2]; ^[3]; Kronenberg, Amy ^[4]; Geurts, Aron ^[1]; Klawikowski, Slade ^[1]; Mattson, David ^[5]; ^[1]

Medical College of Wisconsin, Milwaukee, WI (United States)
New York University, NY (United States)
University of California, Los Angeles, CA (United States)
Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)
Medical College of Georgia, Augusta, GA (United States)

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.

View Accepted Manuscript (DOE)

Research Organization:: Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)

Sponsoring Organization:: National Aeronautics and Space Administration (NASA); USDOE

Grant/Contract Number:: AC02-05CH11231

OSTI ID:: 2470590

Journal Information:: Toxics, Journal Name: Toxics Journal Issue: 12 Vol. 10; ISSN 2305-6304

Publisher:: MDPICopyright Statement

Country of Publication:: United States

Language:: English

References (27)

Non-targeted effects induced by ionizing radiation: Mechanisms and potential impact on radiation induced health effects Morgan, William F.; Sowa, Marianne B. Cancer Letters, Vol. 356, Issue 1 https://doi.org/10.1016/j.canlet.2013.09.009	journal	January 2015
Low-Dose Irradiation Promotes Persistent Oxidative Stress and Decreases Self-Renewal in Hematopoietic Stem Cells Rodrigues-Moreira, Sarah; Moreno, Stéphanie G.; Ghinatti, Giulia Cell Reports, Vol. 20, Issue 13 https://doi.org/10.1016/j.celrep.2017.09.013	journal	September 2017
Defined Sensing Mechanisms and Signaling Pathways Contribute to the Global Inflammatory Gene Expression Output Elicited by Ionizing Radiation Purbey, Prabhat K.; Scumpia, Philip O.; Kim, Peter J. Immunity, Vol. 47, Issue 3 https://doi.org/10.1016/j.immuni.2017.08.017	journal	September 2017
The TGF-β co-receptor endoglin regulates macrophage infiltration and cytokine production in the irradiated mouse kidney Scharpfenecker, Marion; Floot, Ben; Russell, Nicola S. Radiotherapy and Oncology, Vol. 105, Issue 3 https://doi.org/10.1016/j.radonc.2012.08.021	journal	December 2012
Mitotic progression following DNA damage enables pattern recognition within micronuclei Harding, Shane M.; Benci, Joseph L.; Irianto, Jerome Nature, Vol. 548, Issue 7668 https://doi.org/10.1038/nature23470	journal	July 2017
Risk of Ischemic Heart Disease in Women after Radiotherapy for Breast Cancer Darby, Sarah C.; Ewertz, Marianne; McGale, Paul New England Journal of Medicine, Vol. 368, Issue 11 https://doi.org/10.1056/NEJMoa1209825	journal	March 2013
Imaging of radiation effects on cellular 26S proteasome function in situ Brush, James M.; Kim, Kwanghee; Sayre, James W. International Journal of Radiation Biology, Vol. 85, Issue 6 https://doi.org/10.1080/09553000902883794	journal	January 2009
Radiation as a Risk Factor for Cardiovascular Disease Baker, John E.; Moulder, John E.; Hopewell, John W. Antioxidants & Redox Signaling, Vol. 15, Issue 7 https://doi.org/10.1089/ars.2010.3742	journal	October 2011
An analysis of variance test for normality (complete samples) Shapiro, S. S.; Wilk, M. B. Biometrika, Vol. 52, Issue 3-4 https://doi.org/10.1093/biomet/52.3-4.591	journal	December 1965
Irradiation of the kidneys causes pathologic remodeling in the nontargeted heart: A role for the immune system Lenarczyk, Marek; Laiakis, Evagelia C.; Mattson, David L. FASEB BioAdvances, Vol. 2, Issue 12 https://doi.org/10.1096/fba.2020-00071	journal	October 2020
Spatiotemporal immune zonation of the human kidney Stewart, Benjamin J.; Ferdinand, John R.; Young, Matthew D. Science, Vol. 365, Issue 6460 https://doi.org/10.1126/science.aat5031	journal	September 2019
Cardiac outcomes in a cohort of adult survivors of childhood and adolescent cancer: retrospective analysis of the Childhood Cancer Survivor Study cohort Mulrooney, D. A.; Yeazel, M. W.; Kawashima, T. BMJ, Vol. 339, Issue dec08 1 https://doi.org/10.1136/bmj.b4606	journal	December 2009
Renal nerves and leukocyte infiltration in the kidney during salt-sensitive hypertension Alsheikh, Ammar J.; Lund, Hayley; Dasinger, John Henry American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, Vol. 317, Issue 1 https://doi.org/10.1152/ajpregu.00070.2019	journal	July 2019
CD247 Modulates Blood Pressure by Altering T-Lymphocyte Infiltration in the Kidney Rudemiller, Nathan; Lund, Hayley; Jacob, Howard J. Hypertension, Vol. 63, Issue 3 https://doi.org/10.1161/HYPERTENSIONAHA.113.02191	journal	March 2014
Dietary Effects on Dahl Salt-Sensitive Hypertension, Renal Damage, and the T Lymphocyte Transcriptome Abais-Battad, Justine M.; Alsheikh, Ammar J.; Pan, Xiaoqing Hypertension, Vol. 74, Issue 4 https://doi.org/10.1161/HYPERTENSIONAHA.119.12927	journal	October 2019
Radiation‐Induced Cardiovascular Disease: Review of an Underrecognized Pathology Belzile‐Dugas, Eve; Eisenberg, Mark J. Journal of the American Heart Association, Vol. 10, Issue 18 https://doi.org/10.1161/JAHA.121.021686	journal	September 2021
Causes, consequences, and reversal of immune system aging Montecino-Rodriguez, Encarnacion; Berent-Maoz, Beata; Dorshkind, Kenneth Journal of Clinical Investigation, Vol. 123, Issue 3 https://doi.org/10.1172/JCI64096	journal	March 2013
Development of a 2-dimensional atlas of the human kidney with imaging mass cytometry Singh, Nikhil; Avigan, Zachary M.; Kliegel, Judith A. JCI Insight, Vol. 4, Issue 12 https://doi.org/10.1172/jci.insight.129477	journal	June 2019
Rodent Immunohistochemistry: Pitfalls and Troubleshooting Ward, J. M.; Rehg, J. E. Veterinary Pathology, Vol. 51, Issue 1 https://doi.org/10.1177/0300985813503571	journal	September 2013
On a Test of Whether one of Two Random Variables is Stochastically Larger than the Other Mann, H. B.; Whitney, D. R. The Annals of Mathematical Statistics, Vol. 18, Issue 1 https://doi.org/10.1214/aoms/1177730491	journal	March 1947
Whole Body Irradiation—Radiobiology or Medicine? Mole, R. H. The British Journal of Radiology, Vol. 26, Issue 305 https://doi.org/10.1259/0007-1285-26-305-234	journal	May 1953
The Toll-Like Receptor Gene Family Is Integrated into Human DNA Damage and p53 Networks Menendez, Daniel; Shatz, Maria; Azzam, Kathleen PLoS Genetics, Vol. 7, Issue 3 https://doi.org/10.1371/journal.pgen.1001360	journal	March 2011
Involvement of Purinergic Signaling in Cellular Response to γ Radiation Tsukimoto, Mitsutoshi; Homma, Takujiro; Ohshima, Yasuhiro Radiation Research, Vol. 173, Issue 3 https://doi.org/10.1667/RR1732.1	journal	March 2010
A Sense of Danger from Radiation ¹ McBride, William H.; Chiang, Chi-Shiun; Olson, Jennifer L. Radiation Research, Vol. 162, Issue 1 https://doi.org/10.1667/RR3196	journal	July 2004
Cardiac Injury after 10 Gy Total Body Irradiation: Indirect Role of Effects on Abdominal Organs Lenarczyk, Marek; Lam, Vy; Jensen, Eric Radiation Research, Vol. 180, Issue 3 https://doi.org/10.1667/RR3292.1	journal	September 2013
10 Gy total body irradiation increases risk of coronary sclerosis, degeneration of heart structure and function in a rat model Baker, John E.; Fish, Brian L.; Su, Jidong International Journal of Radiation Biology, Vol. 85, Issue 12 https://doi.org/10.3109/09553000903264473	journal	December 2009
Long-Term Cardiac Damage Associated With Abdominal Irradiation in Mice Wang, Zhaojia; Jia, Ziheng; Zhou, Zandong Frontiers in Pharmacology, Vol. 13 https://doi.org/10.3389/fphar.2022.850735	journal	February 2022

Similar Records

Irradiation of the kidneys causes pathologic remodeling in the nontargeted heart: A role for the immune system

Journal Article · Thu Oct 22 20:00:00 EDT 2020 · Geography and Sustainability · OSTI ID:1826902

Exposure to multiple ion beams, broadly representative of galactic cosmic rays, causes perivascular cardiac fibrosis in mature male rats

Journal Article · Tue Apr 25 20:00:00 EDT 2023 · PLoS ONE · OSTI ID:2470768

Simvastatin mitigates increases in risk factors for and the occurrence of cardiac disease following 10 Gy total body irradiation

Journal Article · Sun May 31 20:00:00 EDT 2015 · Pharmacology Research & Perspectives · OSTI ID:1213431

Related Subjects

60 APPLIED LIFE SCIENCES
T cell knock down
cardiac fibrosis
environmental sciences & ecology
heart
immune system
keyword radiation
kidney
nephropathy
rat
toxicology

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

Citation Formats

References (27)

Similar Records

Related Subjects