Human monocyte subtype expression of neuroinflammation and regeneration-related genes is linked to age and sex

Abstract

Stroke is a leading cause of disability and the third cause of death. The immune system plays a pivotal role in post-stroke recovery. After an ischemic stroke, monocytes infiltrate the injured brain tissue and can exacerbate or mitigate the damage. There are sex disparities in ischemic stroke incidence, outcomes, and recovery, and these differences may be hormone-driven and/or determined by genetic and epigenetic factors. Ischemic stroke is more prevalent in the aged population, and the aged brain exhibits an altered immune response. Here, we studied whether peripheral blood human monocyte sub-type (classical, intermediate, and non-classical) expression of inflammation- and regeneration-related genes depends on age and sex. FACS analysis of blood samples from 44 healthy volunteers showed that the numbers of B-cells, NK-cells, T-cells, monocytes, and subtypes of monocytes were not linked to age or sex. Gene expression analysis by qPCR identified several genes differentially correlating with age and sex within different monocyte subtypes. Interestingly, ANXA1 and CD91 showed a consistent increase with aging in all monocyte subtypes and in non-classical and intermediate, respectively. Most age-dependent genes were differentially expressed in females. Our findings show that the gene expression pattern in monocyte subtypes is correlated with age and sex. This may have implications for the characteristics and role of the immune response during the stroke and its contribution to the recovery. Our data might help to understand the role of monocytes in stroke better and support the development of new neuroinflammation modulation-based treatments for stroke patients.