Age-Related Alterations in Peripheral Immune Landscape with Magnified Impact on Post-Stroke Brain

Immunosenescence refers to the multifaceted and profound alterations in the immune system brought about by aging, exerting complex influences on the pathophysiological processes of diseases that manifest upon it. Using a combination of single-cell RNA sequencing, cytometry by time of flight, and var...

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Main Authors: Jianan Lu, Huaming Li, Guoqiang Zhang, Fan Yang, Xiaotao Zhang, An Ping, Zhouhan Xu, Yichen Gu, Rui Wang, Dan Ying, Jianjian Liu, Jianmin Zhang, Ligen Shi
Format: Article
Language:English
Published: American Association for the Advancement of Science (AAAS) 2023-01-01
Series:Research
Online Access:https://spj.science.org/doi/10.34133/research.0287
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author Jianan Lu
Huaming Li
Guoqiang Zhang
Fan Yang
Xiaotao Zhang
An Ping
Zhouhan Xu
Yichen Gu
Rui Wang
Dan Ying
Jianjian Liu
Jianmin Zhang
Ligen Shi
author_facet Jianan Lu
Huaming Li
Guoqiang Zhang
Fan Yang
Xiaotao Zhang
An Ping
Zhouhan Xu
Yichen Gu
Rui Wang
Dan Ying
Jianjian Liu
Jianmin Zhang
Ligen Shi
author_sort Jianan Lu
collection DOAJ
description Immunosenescence refers to the multifaceted and profound alterations in the immune system brought about by aging, exerting complex influences on the pathophysiological processes of diseases that manifest upon it. Using a combination of single-cell RNA sequencing, cytometry by time of flight, and various immunological assays, we investigated the characteristics of immunosenescence in the peripheral blood of aged mice and its impact on the cerebral immune environment after ischemic stroke. Our results revealed some features of immunosenescence. We observed an increase in neutrophil counts, concurrent with accelerated neutrophil aging, characterized by altered expression of aging-associated markers like CD62L and consequential changes in neutrophil-mediated immune functions. Monocytes/macrophages in aged mice exhibited enhanced antigen-presentation capabilities. T cell profiles shifted from naive to effector or memory states, with a specific rise in T helper 1 cells and T helper 17 cells subpopulations and increased regulatory T cell activation in CD4 T cells. Furthermore, regulatory CD8 T cells marked by Klra decreased with aging, while a subpopulation of exhausted-like CD8 T cells expanded, retaining potent immunostimulatory and proinflammatory functions. Critically, these inherent disparities not only persisted but were further amplified within the ischemic hemispheres following stroke. In summary, our comprehensive insights into the key attributes of peripheral immunosenescence provide a vital theoretical foundation for understanding not only ischemic strokes but also other age-associated diseases.
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spelling doaj.art-95c4d43eb375422493c302e53562b10c2024-04-03T08:56:27ZengAmerican Association for the Advancement of Science (AAAS)Research2639-52742023-01-01610.34133/research.0287Age-Related Alterations in Peripheral Immune Landscape with Magnified Impact on Post-Stroke BrainJianan Lu0Huaming Li1Guoqiang Zhang2Fan Yang3Xiaotao Zhang4An Ping5Zhouhan Xu6Yichen Gu7Rui Wang8Dan Ying9Jianjian Liu10Jianmin Zhang11Ligen Shi12Department of Neurosurgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.Department of Neurosurgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.Department of Neurosurgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.Department of Neurosurgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.Department of Neurosurgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.Department of Neurosurgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.Department of Neurosurgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.Department of Neurosurgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.Department of Neurosurgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.Department of Neurosurgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.Department of Neurosurgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.Department of Neurosurgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.Department of Neurosurgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.Immunosenescence refers to the multifaceted and profound alterations in the immune system brought about by aging, exerting complex influences on the pathophysiological processes of diseases that manifest upon it. Using a combination of single-cell RNA sequencing, cytometry by time of flight, and various immunological assays, we investigated the characteristics of immunosenescence in the peripheral blood of aged mice and its impact on the cerebral immune environment after ischemic stroke. Our results revealed some features of immunosenescence. We observed an increase in neutrophil counts, concurrent with accelerated neutrophil aging, characterized by altered expression of aging-associated markers like CD62L and consequential changes in neutrophil-mediated immune functions. Monocytes/macrophages in aged mice exhibited enhanced antigen-presentation capabilities. T cell profiles shifted from naive to effector or memory states, with a specific rise in T helper 1 cells and T helper 17 cells subpopulations and increased regulatory T cell activation in CD4 T cells. Furthermore, regulatory CD8 T cells marked by Klra decreased with aging, while a subpopulation of exhausted-like CD8 T cells expanded, retaining potent immunostimulatory and proinflammatory functions. Critically, these inherent disparities not only persisted but were further amplified within the ischemic hemispheres following stroke. In summary, our comprehensive insights into the key attributes of peripheral immunosenescence provide a vital theoretical foundation for understanding not only ischemic strokes but also other age-associated diseases.https://spj.science.org/doi/10.34133/research.0287
spellingShingle Jianan Lu
Huaming Li
Guoqiang Zhang
Fan Yang
Xiaotao Zhang
An Ping
Zhouhan Xu
Yichen Gu
Rui Wang
Dan Ying
Jianjian Liu
Jianmin Zhang
Ligen Shi
Age-Related Alterations in Peripheral Immune Landscape with Magnified Impact on Post-Stroke Brain
Research
title Age-Related Alterations in Peripheral Immune Landscape with Magnified Impact on Post-Stroke Brain
title_full Age-Related Alterations in Peripheral Immune Landscape with Magnified Impact on Post-Stroke Brain
title_fullStr Age-Related Alterations in Peripheral Immune Landscape with Magnified Impact on Post-Stroke Brain
title_full_unstemmed Age-Related Alterations in Peripheral Immune Landscape with Magnified Impact on Post-Stroke Brain
title_short Age-Related Alterations in Peripheral Immune Landscape with Magnified Impact on Post-Stroke Brain
title_sort age related alterations in peripheral immune landscape with magnified impact on post stroke brain
url https://spj.science.org/doi/10.34133/research.0287
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