Phenotypic and functional alterations of monocyte subsets with aging

Yu Cao; Yang Fan; Fangyuan Li; Yu Hao; Yaxian Kong; Chen Chen; Xing Hao; Dannuo Han; Guoli Li; Zengtao Wang; Chuan Song; Junyan Han; Hui Zeng

doi:10.1186/s12979-022-00321-9

Phenotypic and functional alterations of monocyte subsets with aging

Immun Ageing. 2022 Dec 13;19(1):63. doi: 10.1186/s12979-022-00321-9.

Authors

Yu Cao^{1

2

3}, Yang Fan^{1

2

3}, Fangyuan Li^{4

5}, Yu Hao^{4

5}, Yaxian Kong^{1

2

3}, Chen Chen^{4

5}, Xing Hao⁶, Dannuo Han⁶, Guoli Li^{1

2

3}, Zengtao Wang^{1

2

3}, Chuan Song^{1

2

3}, Junyan Han^{7

8}, Hui Zeng^{9

10

11

12

13}

Affiliations

¹ Beijing Key Laboratory of Emerging Infectious Diseases, Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, China.
² Beijing Institute of Infectious Diseases, Beijing, 100015, China.
³ National Center for Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, China.
⁴ Biomedical Innovation Center, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, China.
⁵ Beijing Key Laboratory for Therapeutic Cancer Vaccines, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, China.
⁶ Center for Cardiac Intensive Care, Beijing Anzhen Hospital, Capital Medical University, Beijing, 100029, China.
⁷ Biomedical Innovation Center, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, China. hanjunyan@ccmu.edu.cn.
⁸ Beijing Key Laboratory for Therapeutic Cancer Vaccines, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, China. hanjunyan@ccmu.edu.cn.
⁹ Beijing Key Laboratory of Emerging Infectious Diseases, Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, China. zenghui@ccmu.edu.cn.
¹⁰ Beijing Institute of Infectious Diseases, Beijing, 100015, China. zenghui@ccmu.edu.cn.
¹¹ National Center for Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, China. zenghui@ccmu.edu.cn.
¹² Biomedical Innovation Center, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, China. zenghui@ccmu.edu.cn.
¹³ Beijing Key Laboratory for Therapeutic Cancer Vaccines, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, China. zenghui@ccmu.edu.cn.

Abstract

Background: It has been widely accepted that monocytes are one of the central mediators contributing to inflammaging. However, it remains unclear whether aged monocytes, similar to aged T cells, have characteristics of hyperactivation and increased expression of co-inhibitory molecules.

Methods: Peripheral blood mononuclear cells (PBMCs) were isolated from young (21-40 years old), middle-aged (41-60 years old), and older human subjects (> 60 years old). Flow cytometry was used to monitor changes in the expression of surface molecules of monocyte subsets and cytokine-producing capacity.

Results: We observed increased tumor necrosis factor-α: TNF-α and decreased interleukin-6 (IL-6) production in monocytes from older adults compared with young and middle-aged adults. Older adults had a greater percentage of intermediate and non-classical monocyte subsets, along with increased levels of the immune activation markers human leukocyte antigen-DR (HLA-DR), and adhesion molecules cluster of differentiation molecule 11b (CD11b) and L-selectin (CD62L). Furthermore, we observed increased C-C motif chemokine receptor 2 (CCR2) expression on classical monocytes and decreased C-X3-C motif chemokine receptor 1 (CX3CR1) expression on non-classical monocytes in older adult subjects. The expression of co-inhibitory receptors was reduced on monocyte subsets in older adults.

Conclusions: Circulating monocytes in older adults exhibit increased expression of activation, adhesion, and migration markers, but decreased expression of co-inhibitory molecules.

Keywords: Activation; Aging; Immunosenescence; Monocytes.