Highly multiplexed immune profiling throughout adulthood reveals kinetics of lymphocyte infiltration in the aging mouse prostate
Abstract
Aging is a significant risk factor for disease 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 immune microenvironment is characteristic of prostatic aging in mice, but whether features of aging in the prostate emerge predominantly in old age or earlier in adulthood has not previously been established. Using highly multiplexed immune profiling and time-course analysis, we tracked the abundance of 29 immune cell clusters in the aging mouse prostate. Early in adulthood, myeloid cells comprise the vast majority of immune cells in the 3-month-old mouse prostate. Between 6 and 12 months of age, there is a profound shift towards a T and B lymphocyte-dominant mouse prostate immune microenvironment. Comparing the prostate to other urogenital tissues, we found similar features of age-related inflammation in the mouse bladder but not the kidney. 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
© 2023 Fox et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Special thanks to the UCLA Jonsson Comprehensive Cancer Center Flow Cytometry Core Facility Staff for CyTOF sample acquisition and Johnny Diaz for sample preparation. We also thank UCLA's Institute for Quantitative and Computational Biology. 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, the UCLA Jonsson Comprehensive Cancer Center and Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research Ablon Scholars Program, 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. 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. T.H. performed IHC experiments and wrote part of 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. The authors declare no conflicts of interest related to this study. All animal experiments were performed using ethical guidelines and protocols approved by the UCLA Animal Research Committee (ARC).Attached Files
Published - aging-v15i9-204708.pdf
Supplemental Material - aging-v15i9-204708-supplementary-material-SD1.pdf
Supplemental Material - aging-v15i9-204708-supplementary-material-SD2.xlsx
Supplemental Material - aging-v15i9-204708-supplementary-material-SD3.pdf
Supplemental Material - aging-v15i9-204708-supplementary-material-SD4.xlsx
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Additional details
- Eprint ID
- 122128
- Resolver ID
- CaltechAUTHORS:20230705-942391700.11
- PMCID
- PMC10449296
- P30 CA016042
- NIH
- 5P30 AI028697
- NIH
- James B. Pendleton Charitable Trust
- UCLA
- Eugene V. Cota-Robles Fellowship
- Spitzer Family Foundation
- RSG-17-068-01-TBG
- American Cancer Society
- W81XWH-13-1-0470
- Department of Defense
- STOP Cancer
- R01CA237191
- NIH
- P50CA092131
- NIH
- Eli and Edythe Broad Foundation
- Rose Hills Foundation
- Created
-
2023-07-25Created from EPrint's datestamp field
- Updated
-
2023-07-25Created from EPrint's last_modified field