Circulating Treg cells from patients with cerebral aneurysms displayed deficiency in ICOS expression and function

Abstract

Inducible costimulator (ICOS) is a member of the CD28 family. When activated, ICOS signalling promotes FOXP3 CNS2 gene demethylation and stabilizes Treg differentiation. Cerebral aneurysm (CA) is the local ballooning of the cerebral vasculature, characterized by higher levels of inflammation mediators and tissue remodelling. FOXP3+ Treg cell dysfunction may contribute to CA pathogenesis. In this study, the expression and function of ICOS in Treg cells was investigated. Circulating CD4+CD25hi T cells from CA subjects demonstrated significantly lower levels of ICOS expression than circulating CD4+CD25hi T cells from healthy subjects. In both healthy subjects and CA subjects, FOXP3+ Treg cells were highly concentrated in the ICOS+ fraction of CD4+CD25hi T cells. Anti‐ICOS costimulation, in combination with anti‐CD3 and IL‐2, significantly increased FOXP3 expression in CD4+CD25hiICOS+ T cells but not in CD4+CD25hiICOS‐ T cells. In addition, anti‐CD3/IL‐2 and anti‐ICOS costimulation significantly elevated the expression of IL‐10 and TGF‐β, decreased the expression of IL‐17, and enhanced CD4+CD25hiICOS+ T cell‐mediated suppression of autologous CD4+CD25‐ Tconv proliferation. Interestingly, CD4+CD25hiICOS+ T cells from CA subjects presented lower responsiveness toward anti‐ICOS costimulation than CD4+CD25hiICOS+ T cells from healthy subjects. Overall, these results demonstrated that ICOS signalling could significantly improve FOXP3 expression and enhance Treg functional potency. However, circulating Treg cells from CA patients displayed reduced ICOS expression and lower responsiveness toward anti‐ICOS stimulation.

High-Dimensional Immune Profiling by Mass Cytometry Revealed the Circulating Immune Cell Landscape in Patients With Intracranial Aneurysm

“…In this study, the imbalance of CD4 + T cell subsets in IA patients was further confirmed, with higher frequencies of C02 (CD27 + CD4 + Tem), C03(HLA-DR + CD4 + Tn), C05(CD27 - CD4 + Tem), and C17 (HLA-DR + CD4 + Tcm), and lower frequencies of C09(HLA-DR - CD4 + Tn), C11(Treg cells), C26(CXCR5 + CD4 + Tem), and C27(HLA-DR - CD4 + Tcm). In addition, recent studies have shown that Treg cells were significantly decreased in IA patients compared with HCs ( 9 , 20 – 22 ) Additionally, the expression leves of Foxp3, and IL-10 were significantly lower in Treg cells from IA patients than from HCs ( 20 – 22 ), which is also consistent with our findings.…”

“…Dysregulation of CD4 + T cells is involved in the pathogenesis of various chronic inflammatory disorders. A previous study demonstrated that IA patients exhibited an imbalance of CD4 + T cell subsets ( 11 , 18 – 20 ). Zhang et al.…”

“…Dysregulation of CD4 + T cells is involved in the pathogenesis of various chronic inflammatory disorders. A previous study demonstrated that IA patients exhibited an imbalance of CD4 + T cell subsets (11,(18)(19)(20). Zhang et al found that the frequencies Th1 and Th17 cells in IA patients were higher, and the frequencies of Th2 and Treg were lower than those in HCs (11).…”