An aging-related immune landscape in the hematopoietic immune system

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Abstract

Background

Aging is a holistic change that has a major impact on the immune system, and immunosenescence contributes to the overall progression of aging. The bone marrow is the most important hematopoietic immune organ, while the spleen, as the most important extramedullary hematopoietic immune organ, maintains homeostasis of the human hematopoietic immune system (HIS) in cooperation with the bone marrow. However, the overall changes in the HIS during aging have not been described. Here, we describe a hematopoietic immune map of the spleen and bone marrow of young and old mice using single-cell sequencing and flow cytometry techniques.

Results

We observed extensive, complex changes in the HIS during aging. Compared with young mice, the immune cells of aged mice showed a marked tendency toward myeloid differentiation, with the neutrophil population accounting for a significant proportion of this response. In this change, hypoxia-inducible factor 1-alpha (Hif1α) was significantly overexpressed, and this enhanced the immune efficacy and inflammatory response of neutrophils. Our research revealed that during the aging process, hematopoietic stem cells undergo significant changes in function and composition, and their polymorphism and differentiation abilities are downregulated. Moreover, we found that the highly responsive CD62L + HSCs were obviously downregulated in aging, suggesting that they may play an important role in the aging process.

Conclusions

Overall, aging extensively alters the cellular composition and function of the HIS. These findings could potentially give high-dimensional insights and enable more accurate functional and developmental analyses as well as immune monitoring in HIS aging.

Supplementary Information

The online version contains supplementary material available at 10.1186/s12979-023-00403-2.

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Author and article information

Contributors

Wenru Su: suwr3@mail.sysu.edu.cn

Journal

Journal ID (nlm-ta): Immun Ageing

Journal ID (iso-abbrev): Immun Ageing

Title: Immunity & Ageing : I & A

Publisher: BioMed Central (London )

ISSN (Electronic): 1742-4933

Publication date (Electronic): 2 January 2024

Publication date PMC-release: 2 January 2024

Publication date Collection: 2024

Volume: 21

Electronic Location Identifier: 3

Affiliations

[1 ]State Key Laboratory of Ophthalmology, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Zhongshan Ophthalmic Center, Sun Yat-Sen University, ( https://ror.org/0064kty71) Guangzhou, 510060 China

[2 ]Department of Ophthalmology, West China Hospital, Sichuan University, ( https://ror.org/011ashp19) Chengdu, 610041 Sichuan China

Article

Publisher ID: 403

DOI: 10.1186/s12979-023-00403-2

PMC ID: 10759628

PubMed ID: 38169405

SO-VID: 71942ee3-71ad-4dc7-82f4-b04c4a0b1e1d

License:

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

History

Date received : 31 August 2023

Date accepted : 11 December 2023

Custom metadata

ScienceOpen disciplines: Immunology

Keywords: hematopoietic immune system,neutrophils,aging,spleen,bone marrow,myeloid cells,hematopoietic stem cells,single-cell sequencing,single-cell flow cytometry

Data availability:

ScienceOpen disciplines: Immunology

Keywords: hematopoietic immune system, neutrophils, aging, spleen, bone marrow, myeloid cells, hematopoietic stem cells, single-cell sequencing, single-cell flow cytometry

An aging-related immune landscape in the hematopoietic immune system

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Abstract

Background

Results

Conclusions

Supplementary Information

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Most cited references 75

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Fast, sensitive, and accurate integration of single cell data with Harmony

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