Characteristics of circulating monocytes at baseline and after activation in patients with intracranial aneurysm

Intracranial aneurysm (IA) is a bulging of blood vessels around the brain that is often asymptomatic but may cause severe complications and death if ruptured. Macrophage-mediated immune responses can contribute to the development of IA. During homeostasis and inflammation, circulating monocytes can infiltrate the vasculature, where they develop into macrophages, and modulate immune responses. Based on the expression of CD14 and CD16, total circulating monocytes can be distinguished into three main subsets, including the CD14⁺CD16^- classical monocytes, the CD14⁺CD16⁺ intermediate monocytes, and the CD14^loCD16⁺⁺ non-classical monocytes. In this study, we found that frequencies of CD14⁺CD16^- classical monocytes were significantly lower in IA patients than in healthy controls, while the frequencies of CD14⁺CD16⁺ intermediate monocytes and CD14^loCD16⁺⁺ non-classical monocytes were significantly higher in IA patients than in healthy controls. The frequencies of CD14⁺CD16⁺ intermediate monocytes were further elevated in IA-ruptured patients compared to those in IA-unruptured patients. Compared to classical monocytes, intermediate monocytes and non-classical monocytes presented higher TNF-α and IL-1β expression. When cocultured with autologous naive CD4 T cells, intermediate and non-classical monocytes preferentially promoted the expression of TBX21 and RORC over the expression of FOXP3 in CD4 T cells. Inhibition of TNF-α and IL-1β slightly reduced TBX21 expression and markedly reduced RORC expression, and at the same time significantly increased FOXP3 expression in CD4 T cells. Overall, this study demonstrated that the monocytes were dysregulated in IA patients in a manner that favored the development of proinflammatory responses.