Production of MHCII-expressing classical monocytes increases during aging in mice and humans

Pijus K Barman; Juliana E Shin; Sloan A Lewis; Seokjo Kang; Di Wu; Yizhou Wang; Xiaoming Yang; Prakash S Nagarkatti; Mitzi Nagarkatti; Ilhem Messaoudi; Bérénice A Benayoun; Helen S Goodridge

doi:10.1111/acel.13701

Production of MHCII-expressing classical monocytes increases during aging in mice and humans

Aging Cell. 2022 Oct;21(10):e13701. doi: 10.1111/acel.13701. Epub 2022 Aug 30.

Authors

Pijus K Barman^{1

2}, Juliana E Shin^{1

2}, Sloan A Lewis^{3

4}, Seokjo Kang^{1

2}, Di Wu⁵, Yizhou Wang⁵, Xiaoming Yang⁶, Prakash S Nagarkatti⁶, Mitzi Nagarkatti⁶, Ilhem Messaoudi^{3

4

7}, Bérénice A Benayoun^{8

9

10}, Helen S Goodridge^{1

2}

Affiliations

¹ Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA.
² Research Division of Immunology in the Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, California, USA.
³ Department of Molecular Biology and Biochemistry, University of California, Irvine, California, USA.
⁴ Institute for Immunology, University of California, Irvine, California, USA.
⁵ Applied Genomics, Computation and Translational Core, Cedars-Sinai Cancer, Cedars-Sinai Medical Center, Los Angeles, California, USA.
⁶ Department of Pathology, Microbiology and Immunology, School of Medicine, University of South Carolina, Columbia, South Carolina, USA.
⁷ Department of Microbiology, Immunology and Molecular Genetics in the College of Medicine, University of Kentucky, Lexington, Kentucky, USA.
⁸ Leonard Davis School of Gerontology, University of Southern California, Los Angeles, California, USA.
⁹ Molecular and Computational Biology Department, USC Dornsife College of Letters, Arts and Sciences, University of Southern California, Los Angeles, California, USA.
¹⁰ Biochemistry and Molecular Medicine Department, USC Keck School of Medicine, University of Southern California, Los Angeles, California, USA.

Abstract

Aging is associated with increased monocyte production and altered monocyte function. Classical monocytes are heterogenous and a shift in their subset composition may underlie some of their apparent functional changes during aging. We have previously shown that mouse granulocyte-monocyte progenitors (GMPs) produce "neutrophil-like" monocytes (NeuMo), whereas monocyte-dendritic cell progenitors (MDPs) produce monocyte-derived dendritic cell (moDC)-producing monocytes (DCMo). Here, we demonstrate that classical monocytes from the bone marrow of old male and female mice have higher expression of DCMo signature genes (H2-Aa, H2-Ab1, H2-Eb1, Cd74), and that more classical monocytes express MHCII and CD74 protein. Moreover, we show that bone marrow MDPs and classical monocytes from old mice yield more moDC. We also demonstrate higher expression of Aw112010 in old monocytes and that Aw112010 lncRNA activity regulates MHCII induction in macrophages, which suggests that elevated Aw112010 levels may underlie increased MHCII expression during monocyte aging. Finally, we show that classical monocyte expression of MHCII is also elevated during healthy aging in humans. Thus, aging-associated changes in monocyte production may underlie altered monocyte function and have implications for aging-associated disorders.

Keywords: aging; bone marrow progenitors; monocytes.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cell Differentiation
Dendritic Cells
Female
Histocompatibility Antigens Class II
Humans
Macrophages
Male
Mice
Monocytes* / metabolism
RNA, Long Noncoding* / metabolism

Substances

RNA, Long Noncoding
Histocompatibility Antigens Class II

Abstract

Publication types

MeSH terms

Substances

Grants and funding