Highly multiplexed immune profiling throughout adulthood reveals kinetics of lymphocyte infiltration in the aging mouse prostate

Creators: Fox, Jonathan J.; Hashimoto, Takao; Navarro, Héctor I.; Garcia, Alejandro J.; Shou, Benjamin L.; Goldstein, Andrew S.

Abstract

Aging is a significant risk factor for cancer in several tissues, including the prostate. Defining the kinetics of age-related changes in these tissues is critical for identifying regulators of aging and evaluating interventions to slow the aging process and reduce disease risk. An altered microenvironment is characteristic of prostatic aging in mice. Whether features of aging in the prostate emerge predominantly in old age or earlier in adulthood has not previously been established. Using comprehensive immune profiling and time-course analysis, we show that populations of T and B lymphocytes increase in the mouse prostate between 6 and 12 months of age. When comparing the prostate to other urogenital tissues, we found similar features of age-related inflammation in the mouse bladder. In summary, our study offers new insight into the kinetics of prostatic inflammaging and the window when interventions to slow down age-related changes may be most effective.

Additional Information

The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license. Special thanks to Miriam Guemes for CyTOF sample acquisition and Johnny Diaz for sample preparation. Mass cytometry was performed in the UCLA Jonsson Comprehensive Cancer Center (JCCC) and Center for AIDS Research Flow Cytometry Core Facility which is supported by NIH awards P30 CA016042 and 5P30 AI028697. The purchase of the Helios mass cytometer that was used in this work was, in part, supported by funds provided by the James B. Pendleton Charitable Trust. J.J.F. was supported by scholarships from the UCLA Minor in Biomedical Research and the Silva Endowment as part of the Undergraduate Research Scholars Program at UCLA. H.I.N. was supported by the Eugene V. Cota-Robles Fellowship. A.S.G. is supported by the Spitzer Family Foundation Fund and the Gill Endowment. This work was supported by the American Cancer Society (RSG-17-068-01-TBG), U.S. Department of Defense (W81XWH-13-1-0470), STOP CANCER, NIH/NCI (R01CA237191 and P50CA092131/UCLA SPORE in Prostate Cancer), UCLA Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research Rose Hills Foundation Innovator Grant, and support from UCLA's Jonsson Comprehensive Cancer Center, Broad Stem Cell Research Center, Clinical and Translational Science Institute, and the Institute of Urologic Oncology. We also thank UCLA's Institute for Quantitative and Computational Biology. AUTHOR CONTRIBUTIONS: J.J.F., T.H., H.I.N., and A.S.G. conducted the experiments. J.J.F., H.I.N., and A.S.G. designed the experiments. J.J.F. analyzed flow cytometry and mass cytometry data. J.J.F. and A.S.G. wrote and edited the manuscript. A.J.G. assisted with CyTOF samples and wrote part of the manuscript. B.L.S. performed principal component analysis and wrote part of the manuscript. A.S.G. procured funding and supervised the experiments. Data and Code Availability: The mass cytometry data supporting the current study has not been deposited in a public repository but is available from the corresponding author upon request. RESOURCE AVAILABILITY: Lead Contact - Further information and requests for resources and reagents should be directed to and will be fulfilled by the Lead Contact, Andrew S. Goldstein (agoldstein{at}mednet.ucla.edu). Materials Availability: This study did not generate new unique reagents. The authors declare no competing interests.

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Submitted - 2020.06.18.160556v1.full.pdf

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